bluuebunny/crossref_metadata_2025 huggingface dataset:
Conventional T-bet+Foxp3− Th1 cells are the major source of host-protective regulatory IL-10 during intracellular protozoan infection
Authors: Jankovic Dragana , Kullberg Marika C. , Feng Carl G. , Goldszmid Romina S. , Collazo Carmen M. , Wilson Mark , Wynn Thomas A. , Kamanaka Masahito , Flavell Richard A. , Sher Alan
Published: February 2007

Although interferon γ (IFN-γ) secretion is essential for control of most intracellular pathogens, host survival often also depends on the expression of interleukin 10 (IL-10), a cytokine known to counteract IFN-γ effector functions. We analyzed the source of regulatory IL-10 in mice infected with the protozoan parasite Toxoplasma gondii. Unexpectedly, IFN-γ–secreting T-bet+Foxp3− T helper type 1 (Th1) cells were found to be the major producers of IL-10 in these animals. Further analysis revealed that the same IL-10+IFN-γγ population displayed potent effector function against the parasite while, paradoxically, also inducing profound suppression of IL-12 production by antigen-presenting cells. Although at any given time point only a fraction of the cells appeared to simultaneously produce IL-10 and IFN-γ, IL-10 production could be stimulated in IL-10−IFN-γ+ cells by further activation in vitro. In addition, experiments with T. gondii–specific IL-10+IFN-γ+ CD4 clones revealed that although IFN-γ expression is imprinted and triggered with similar kinetics regardless of the state of Th1 cell activation, IL-10 secretion is induced more rapidly from recently activated than from resting cells. These findings indicate that IL-10 production by CD4+ T lymphocytes need not involve a distinct regulatory Th cell subset but can be generated in Th1 cells as part of the effector response to intracellular pathogens.
The intracellular region of FXYD1 is sufficient to regulate cardiac Na/K ATPase
Authors: Pavlovic Davor , Fuller William , Shattock Michael J.
Published: February 2007

ABSTRACT FXYD1 is a transmembrane protein predominantly expressed in excitable tissues that associates with and regulates Na/K ATPase. PKA phosphorylates FXYD1 at serine 68 (S68), however, the effects of phosphorylation on Na/K ATPase activity are not fully characterized. The objectives of this study were to characterize Na/K ATPase currents in FXYD1 wild‐type (WT) and knockout (KO) adult mouse ventricular myocytes, and investigate the effects of FXYD1 on Na/K ATPase currents using the whole‐cell patch‐clamp technique. A peptide representing the 19 C‐terminal residues of FXYD1 (FXYD154–72) was introduced into the interior of FXYD1 KO and WT myocytes through the patch pipette. K‐sensitive Na/K ATPase currents were higher in KO myocytes (2.9 ±0.1 pA/pF; n=4) compared with WT (1.9±0.1 pA/pF;n=4). Unphosphorylated FXYD154–72, at a concentration of 4 μM, reduced the currents in WT (from 2.1 ±0.1 to 1.3±0.1 pA/pF;P<0.05, n=7) and KO (from 2.9±0.1 to 1.7±0.1 pA/pF;P<0.05, n=5), whereas, 1 μMof FXYD1 54‐72 phosphorylated at S68 increased currents in WT (from 1.91±0.09 to 3.1±0.5 pA/pF;P<0.05, n=6) and KO (from 2.7±0.11 to 3.8±0.2 pA/pF; P<0.05, n=6) myocytes. Coimmunoprecipitation studies demonstrated that S68 phosphorylated and unphosphorylated FXYD154–72 associates with Na/K ATPase α1 subunit. We conclude that unphosphorylated FXYD1 inhibits Na/K ATPase, whereas S68 phosphorylated FXYD1 stimulates Na/K ATPase to a level above that seen in the absence of FXYD1.—Pavlovic, D., Fuller, W., and Shattock, M. J. The intracellular region of FXYD1 is sufficient to regulate cardiac Na/K ATPase. FASEB J. 21, 1539–1546 (2007)
Thalidomide induces limb deformities by perturbing the Bmp/Dkkl/Wnt signaling pathway
Authors: Knobloch Jürgen , Shaughnessy John D. , Rüther Ulrich
Published: February 2007

Thalidomide, a sedative originally used to treat morning sickness and now used to treat leprosy and multiple myeloma, is also a teratogen that induces birth defects in humans such as limb truncations and microphthalmia. However, the teratogenic mechanism of action of this drug remains obscure. Thalidomide induces limb and eye defects in the chicken embryo at an EC50 of 50 μg/kg egg wt and apoptosis in primary human embryonic fibroblasts (HEFs) at an EC50 of 8.9 μM. Using these model systems, we demonstrate by semiquantitative reverse transcriptase‐polymerase chain reaction and whole‐mount in situ hybridization that thalidomide‐induced oxidative stress enhances signaling through bone morphogenetic proteins (Bmps). This leads to up‐regulation of the Bmp target gene and Wnt antagonist Dickkopfl (Dkkl) with subsequent inhibition of canonical Wnt/β‐catenin signaling and increased cell death as shown by trypan blue and terminal deoxynucleotidyl transferase‐mediated nick end labeling staining. Thalidomide‐induced cell death was dra‐matically reduced in HEFs and in embryonic limb buds by the use of inhibitors against Bmps, Dkkl, and Gsk3β,a β‐catenin antagonist acting downstream of Dkkl in the Wnt pathway. Most interestingly, blocking of Dkkl or Gsk3β dramatically counteracts thalido‐mide‐induced limb truncations and microphthalmia. From this, we conclude that perturbing of Bmp/Dkkl/ Wnt signaling is central to the teratogenic effects of thalidomide.—Knobloch, J., Shaughnessy, Jr., J. D., Rüther, U. Thalidomide induces limb deformities by perturbing the Bmp/Dkkl/Wnt signaling pathway FASEB J. 21, 1410–1421 (2007)
Determinants of local spider (Araneidae and Thomisidae) species richness on a regional scale: climate and altitude vs. habitat structure
Authors: JIMÉNEZ‐VALVERDE ALBERTO , LOBO JORGE M.
Published: February 2007

Abstract 1. The habitat heterogeneity hypothesis states that the more complex the habitat, the higher the species richness. The present study analyzes the effect of local factors on regional spider (Araneidae and Thomisidae) richness. The main objective is to disentangle the relative importance of habitat structure and other environmental variables.

2. Fifteen territorial units of 1 km2 were sampled to obtain reliable and comparable inventories of the two spider families. Richness values were modelled using general regression models and a set of climate, topographic and vegetation structure variables. Pure and joint effects were computed via variation partitioning.

3. The results highlight the great importance of vegetation complexity, especially of grass and sub‐shrub cover, in determining spider species richness.

4. The maximum temperature is the only climate variable significantly related to species richness, although its effect is combined with that of spatial and vegetation structure variables.

5. These results support the habitat heterogeneity hypothesis, and highlight the importance of taking vegetation complexity into account when managing habitats and where spider conservation is desired.
Keeping nurses working: development and psychometric testing of the Nurse‐Work Instability Scale (Nurse‐WIS)
Authors: Gilworth Gill , Bhakta Bipin , Eyres Sophie , Carey Amy , Anne Chamberlain M. , Tennant Alan
Published: February 2007

Aim.  This paper reports a study to develop and test the psychometric properties of the Nurse‐Work Instability Scale (Nurse‐WIS).

Background.  Work Instability describes the extent of any mismatch among functional (in)capacity, work demands and its potential impact on efficiency/productivity at work. Recruitment, retention and migration of nurses are global issues influenced by many factors. It is well documented that musculoskeletal pain and subsequent disability account for a high proportion of sickness absence and premature retirement in the nursing workforce. The challenge to clinicians is to identify such problems early so that appropriate interventions can be targeted to facilitate job retention.

Method.  Analyses of 48 qualitative interview transcripts conducted with nursing staff during 2003 were used to generate potential items for the Nurse‐WIS. Analysis of the psychometric properties of the scale derived from these items was undertaken by using the Rasch model and data generated in postal surveys in 2004. The scale was validated against a gold standard of expert vocational assessment by occupational health physiotherapists/ergonomists.

Findings.  The resulting self‐administered questionnaire consisting of 30 items not only measures the risk of job loss relating to musculoskeletal symptoms, but also captures relevant psychosocial issues. The scaling properties of this questionnaire meet the rigorous psychometric requirements of the Rasch model.

Conclusions.  The Nurse‐WIS is a psychometrically sound method for the early identification of nursing staff experiencing difficulties at work. It offers the prospect of positive proactive management to prevent or minimize sickness absence and potentially prevent loss of nursing staff from the workforce through long‐term sickness absence and early retirement.
Recording of drug allergies: are we doing enough?
Authors: Radford Anna , Undre Shabnam , Alkhamesi Nawar A. , Darzi Sir Ara W.
Published: February 2007

Objective  To assess the implementation of local and national guidelines concerning documentation of drug/clinical hypersensitivities.

Design  Audit with retrospective and prospective components used to assess the process of drug hypersensitivity documentation.

Patients  Fifty surgical inpatients’ notes were retrospectively analysed followed by 63 patients prospectively.

Setting  West London teaching hospital.

Main outcome measures  Drug hypersensitivity status correctly indicated on clinical notes, drug ‘Kardex’ charts, and anaesthetic records; these three documents were to concur. Hypersensitivities qualified according to symptoms experienced.

Recommendations  Standardization of preoperative clinical notes and multidisciplinary responsibility for records between doctor, nurse and pharmacist.

Results  Hypersensitivity documentation in clinical notes improved by 7% after the introduction of a formalized history sheet for preoperative clinics. These were based upon the anaesthetic charts, which had demonstrated 100% documentation previously. Considerable improvements (70.8%) in the clarification of adverse reaction symptoms post recommendation were shown; this was also attributed to the new history sheet. Concurrence improved by 2%.

Conclusions  The original study revealed areas for improvement and provided part of the solution – a more standardized preoperative assessment tool. Multidisciplinary cooperation in addition to formalizing the assessment process has led to a more efficient and safer service for patient and medicolegally for health care professionals.

Key messages  (1) Standardized forms, for the recording of clinical information preoperatively, ensure relevant guidelines are implemented in practice. (2) Multidisciplinary teams provide a vital safety net for their patients and colleagues.
Physiological Studies of Stress Responses in the Hypothalamus of Vasopressin‐Enhanced Green Fluorescent Protein Transgenic Rat
Authors: Shibata M. , Fujihara H. , Suzuki H. , Ozawa H. , Kawata M. , Dayanithi G. , Murphy D. , Ueta Y.
Published: February 2007

Arginine vasopressin (AVP) plays an important role in stress‐induced activation of the hypothalamic‐pituitary adrenal axis. In the present study, AVP‐enhanced green fluorescent protein (eGFP) transgenic rats were used to investigate changes in AVP‐eGFP expression in the hypothalamic paraventricular nucleus (PVN) and the median eminence (ME) upon exposure to stress conditions. The eGFP fluorescence in the parvocellular division of the PVN (pPVN) was markedly increased 5 days after bilateral adrenalectomy (ADX) and it was colocalised with corticotrophin‐releasing hormone‐like immunoreactivity in the pPVN. Peripheral administration of dexamethasone completely suppressed the increase of eGFP fluorescence in the pPVN and the external layer of the ME (eME) after bilateral ADX. Significant increases of eGFP fluorescence were observed in the pPVN 6, 12, 24 and 48 h after intraperitoneal (i.p.) administration of lipopolysaccharide (LPS). In the eME, eGFP fluorescence was significantly increased 48 h after i.p. administration of LPS. By contrast, eGFP fluorescence changed neither in the magnocellular division of the PVN, nor the internal layer of the ME after i.p. administration of LPS. Our results indicate that AVP‐eGFP transgenic rats are useful animal model to study dynamic changes of AVP expression in the hypothalamus under stressful conditions.
Comparison of shade matching by visual observation and an intraoral dental colorimeter
Authors: LI Q. , WANG Y. N.
Published: February 2007

Summary  The purpose of this study was to compare the applicability of two shade‐matching approaches: Vintage Halo shade guide (visual method) and Shofu ShadeEye NCC colorimeter (instrumental method). Twenty participants’ maxillary left central incisors were evaluated. Corresponding metal ceramic crowns were fabricated with each shade‐matching approach. The colour distributions (L*, a* and b*) of the middle third region of each tooth and corresponding metal ceramic crowns were spectrophotometrically assessed. The colour difference (ΔE) and colour distributions (ΔL*, Δa* and Δb*) between the tooth and the corresponding crowns were calculated. We found that the colour differences of both groups fell within the clinical unacceptable range (ΔE > 2·75). Regarding ΔE and the three colour distributions, no significant difference was found, expect for a* (P < 0·01). The shade matching difficulty degree was analysed through the agreements of visual shade selection. Within easy matching cases, the instrumental method achieved better results (P = 0·041). In conclusion, it is suggested that the reliability of shade matching can be ensured by neither the colorimeter nor the visual approach. However, the colorimeter can achieve better results within easy matching cases.
Effects of pH and nitrogen forms on expression profiles of genes involved in iron homeostasis in tomato
Authors: ZHAO TING , LING HONG‐QING
Published: February 2007

In this work, we investigated the effects of pH and nitrogen forms on iron homeostasis and the expression profiles of genes involved in iron uptake and metabolism using tomato cultivar T3238 and its iron‐inefficient mutant T3238fer. We showed that high external pH led to increased expression of four iron uptake genes (LeIRT1, LeIRT2, LeFRO1, LeNRAMP1) regardless of the nitrogen sources. Interestingly, the transcript level of FER was decreased at high pH and increased at low pH. In iron‐inefficient mutant T3238fer, the expression of LeFRO1, LeIRT1 and LeNRAMP1 was much less than wild type under the culture conditions with high pH and on the non‐buffered agar medium with NO3‐ as the sole N source, demonstrating that FER protein is required for the increased expression of LeFRO1, LeIRT1 and LeNRAMP1 under culture conditions with high pH. Considering the paradoxical expression patterns of FER to LeFRO1, LeIRT1 and LeNRAMP1 in T3238, we speculate that FER is essential, but is not the limited factor for the transcriptional regulation of the three iron uptake genes. In conclusion, the alteration of rhizosphere pH by assimilating NO3‐ or NH4+ influenced Fe availability and consequently affected iron homeostasis in tomato. The enhanced expression of LeFRO1, LeIRT1 and LeNRAMP1 under the culture condition with high pH or on agar media with NO3‐ as the sole N source might be a consequence of reduced iron availability in the solution or agar medium at high pH.
Development of a semiselective medium for isolating Xanthomonas campestris pv. musacearum from insect vectors, infected plant material and soil
Authors: Mwangi M. , Mwebaze M. , Bandyopadhyay R. , Aritua V. , Eden‐Green S. , Tushemereirwe W. , Smith J.
Published: February 2007

A semiselective medium was developed for isolating Xanthomonas campestris pv. musacearum (Xcm) from infected banana plants, soil and insect vectors. The new medium was named cellobiose‐cephalexin agar (CCA) and it contained (L−1): 1 g yeast extract, 1 g glucose, 1 g peptone, 1 g NH4Cl, 1 g MgSO4·7H2O, 3 g K2HPO4, 1 g beef extract, 10 g cellobiose, 14 g agar, 40 mg cephalexin, 10 mg 5‐fluorouracil and 120 mg cycloheximide. The medium was evaluated for selectivity using 21 bacterial isolates and for plating efficiency using Xcm. The bacterial isolates included a soilborne Xanthomonas species and three pathogenic Xanthomonas strains that infect cassava, cabbage and beans. Although the plating efficiency of Xcm on CCA was lower (59%) than on non‐selective yeast extract peptone glucose agar (YPGA), its selectivity was significantly higher, averaging 60 and 82%, when isolating from banana fruits and soil, respectively. CCA was also superior when isolating Xcm from insect vectors, with selectivity of 48–75%, compared with 8–17% on YPGA. Xanthomonas campestris pv. phaseoli did not grow on CCA, while X. campestris pv. campestris and X. axonopodis pv. manihotis grew, but their colonies were smaller than those of Xcm. Twenty‐nine out of 33 suspected Xcm strains isolated from plants, soil and insects using CCA were pathogenic when inoculated onto banana plants, indicating that CCA can be a reliable tool in isolating Xcm populations. The medium should prove useful in studies on ecology, epidemiology and management of the banana bacterial wilt pathogen that is currently ravaging bananas in East and Central Africa.
Genetic characterization by fluorescent AFLP of Pseudomonas savastanoi pv. savastanoi strains isolated from different host species
Authors: Sisto A. , Cipriani M. G. , Tegli S. , Cerboneschi M. , Stea G. , Santilli E.
Published: February 2007

The genetic diversity of 71 Pseudomonas savastanoi pv. savastanoi strains isolated from different host species and from diverse geographical regions was determined by fluorescent amplified fragment length polymorphism (f‐AFLP) analysis. The study was carried out using three different selective primer combinations. Strains of P. syringae pv. syringae, P. syringae pv. phaseolicola, P. syringae pv. glycinea, P. syringae pv. tagetis and P. amygdali were also included as outgroups. Based on cluster analysis of f‐AFLP data, all P. savastanoi pv. savastanoi strains showed a high degree of similarity, grouping in a cluster and forming a taxon clearly separate from outgroup strains. AFLP analyses failed to support placing strains of P. savastanoi pv. savastanoi, P. syringae pv. phaseolicola and P. syringae pv. glycinea in the same species. Strains of P. savastanoi pv. savastanoi formed subclusters that correlated with the host species. Strains identified within these subclusters were related to the geographical region where the strains were isolated. Strains of P. savastanoi pv. savastanoi from olive were divided into two subclusters. Strains from oleander were differentiated from those from ash and were divided into two additional subclusters, distinct from olive strains. Three strains isolated from jasmine showed a high level of similarity among them but, at a lower Dice similarity coefficient, were linked to a subcluster including olive strains. Finally, two strains isolated from privet were similar to strains from olive and were included in the same subcluster.
Ecological Predictors of Range Areas and Use of Burrow Systems in the Diurnal Rodent, Octodon degus
Authors: Hayes Loren D. , Chesh Adrian S. , Ebensperger Luis A.
Published: February 2007

Variation in animal space use patterns may be linked to numerous ecological factors affecting survival and reproduction. We examined the relationship between ecology and above‐ and below‐ground components of space use by Octodon degus, a semi‐fossorial rodent in Chile. We monitored the daytime minimum convex polygon and adaptive kernel range areas of 26 individuals and determined the number of burrow systems used by degus during night‐time radiotelemetry and trapping of burrow systems on two study grids at Rinconada de Maipú, a semi‐arid Matorral in central Chile. We quantified food biomass, soil hardness, distance to overhead vegetative cover, and density of burrow openings at putative nest burrows. Degus living on the grid with more shrub cover had larger range areas than degus living on the grid with less cover. The range areas of degus decreased with increasing distance from overhead vegetative cover. There was a weak (but statistically significant) negative relationship between the number of burrow systems used by degus and the distance to vegetative cover and density of burrow openings at burrow systems. Male and female degus had similar range areas. Our results suggest that overhead cover decreases the risk of predation to male and female degus. Degus probably balance the benefits of numerous burrow openings (reduced predation risk) with time and energy requirements of burrow construction and maintenance. Models of space use that consider the effect of multiple ecological variables should measure different dimensions of space use.
Bovine Follicular Fluid Contains Antagonist Activity for Cumulus Expansion Promoting Effect by Epidermal Growth Factor
Authors: Hosoda K , Terada T
Published: February 2007

Contents

The present study was conducted to investigate the effects of bovine follicular fluid (bFF) fractions or epidermal growth factor (EGF) on cumulus cell expansion in bovine cumulus–oocyte complexes (COCs) in vitro. bFF derived from large follicles (15–20 mm) and its fractions (>100, 10–100 and <100 kDa) were added to the medium. Cumulus cell expansion was stimulated when COCs were incubated with the 10–100 and <100 kDa fractions or bFF; in contrast, the culture of COCs with the >100 kDa fraction resulted in the suppression of cumulus cell expansion. Although the >100 kDa fraction prohibited the expansion of cumulus cells in the medium with or without low concentration EGF, cumulus expansion was promoted when COCs were cultured with the >100 kDa fraction and high‐concentration EGF. In conclusion, the results suggest that bFF contains promoting and inhibiting effect for expansion of cumulus cells in COCs in vitro. The inhibiting effect of bFF may act antagonistically against the effect of EGF for the event of expanding cumulus cells.
Collective Choice and Control Rights in Firms
Authors: DOW GREGORY K. , SKILLMAN GILBERT L.
Published: February 2007

Recent writers have asserted that firms controlled by workers are rare because workers have diverse preferences over firm policies, while investors all support wealth maximization. However, the source of the asymmetry between capital and labor remains unclear. We resolve this puzzle by arguing that because financial capital is exceptionally mobile, capital markets induce unanimity. The lower mobility of human capital implies that labor markets are monopolistically competitive and hence that unanimity cannot be expected in labor‐managed firms. Moreover, such firms are vulnerable to takeover by investors, while capital‐managed firms are substantially less vulnerable to takeover by workers.
Monetary Policy and Asset Prices: More Bad News for ‘Benign Neglect’*
Authors: Berger Wolfram , Kißmer Friedrich , Wagner Helmut
Published: February 2007

In this paper we explore the optimal policy reaction to boom–bust cycles in asset prices. Bordo and Jeanne (2002a, b) point to the risks of a reactive strategy that only mitigates the consequences of a crisis if and when it occurs. Acting pre‐emptively by rigorously counteracting the build‐up of the crisis scenario may be superior in welfare terms. We show that even a purely reactive monetary policy must involve an ex ante response to a possible asset price crash. The reason, however, is not the attempt to avoid real and financial disruption but to react optimally to changes in the private sector's expectations. Furthermore, we find that the welfare losses of a reactive strategy increase when forward‐looking expectations are taken into account, while the welfare implications of a proactive strategy do not change.
Gene expression changes in long‐term culture of T‐cell clones: genomic effects of chronic antigenic stress in aging and immunosenescence
Authors: Mazzatti Dawn J. , White Andrew , Forsey Rosalyn J. , Powell Jonathan R. , Pawelec Graham
Published: February 2007

The adaptive immune response requires waves of T‐cell clonal expansion on contact with altered self and contraction after elimination of antigen. In the case of persisting antigen, as occurs for example in cytomegalovirus or Epstein–Barr virus infection, this critical process can become dysregulated and responding T‐cells enter into a dysfunctional senescent state. Longitudinal studies suggest that the presence of increased numbers of such T‐cells is a poor prognostic factor for survival in the very elderly. Understanding the nature of the defects in these T‐cells might facilitate intervention to improve immunity in the elderly. The process of clonal expansion under chronic antigenic stress can be modelled in vitro using continuously cultured T‐cells. Here, we have used cDNA array technology to investigate differences in gene expression in a set of five different T‐cell clones at early, middle and late passage in culture. Differentially expressed genes were confirmed by real‐time polymerase chain reaction, and relationships between these assessed using Ingenuity Systems evidence‐based association analysis. Several genes and chemokines related to induction of apoptosis and signal transduction pathways regulated by transforming growth factor β (TGFβ), epidermal growth factor (EGF), fos and β‐catenin were altered in late compared to early passage cells. These pathways and affected genes may play a significant role in driving the cellular senescent phenotype and warrant further investigation as potential biomarkers of aging and senescence. These genes may additionally provide targets for intervention.
Primary laminopathy fibroblasts display altered genome organization and apoptosis
Authors: Meaburn Karen J. , Cabuy Erik , Bonne Gisele , Levy Nicolas , Morris Glenn E. , Novelli Giuseppe , Kill Ian R. , Bridger Joanna M.
Published: February 2007

A number of diseases associated with specific tissue degeneration and premature aging have mutations in the nuclear envelope proteins A‐type lamins or emerin. Those diseases with A‐type lamin mutation are inclusively termed laminopathies. Due to various hypothetical roles of nuclear envelope proteins in genome function we investigated whether alterations to normal genomic behaviour are apparent in cells with mutations in A‐type lamins and emerin. Even though the distributions of these proteins in proliferating laminopathy fibroblasts appear normal, there is abnormal nuclear positioning of both chromosome 18 and 13 territories, from the nuclear periphery to the interior. This genomic organization mimics that found in normal nonproliferating quiescent or senescent cells. This finding is supported by distributions of modified pRb in the laminopathy cells. All laminopathy cell lines tested and an X‐linked Emery–Dreifuss muscular dystrophy cell line also demonstrate increased incidences of apoptosis. The most extreme cases of apoptosis occur in cells derived from diseases with mutations in the tail region of the LMNA gene, such as Dunningan‐type familial partial lipodystrophy and mandibuloacral dysplasia, and this correlates with a significant level of micronucleation in these cells.
Dramatic age‐related changes in nuclear and genome copy number in the nematode Caenorhabditis elegans
Authors: Golden Tamara R. , Beckman Kenneth B. , Lee Andreia H. J. , Dudek Nancy , Hubbard Alan , Samper Enrique , Melov Simon
Published: February 2007

The nematode Caenorhabditis elegans has become one of the most widely used model systems for the study of aging, yet very little is known about how C. elegans age. The development of the worm, from egg to young adult has been completely mapped at the cellular level, but such detailed studies have not been extended throughout the adult lifespan. Numerous single gene mutations, drug treatments and environmental manipulations have been found to extend worm lifespan. To interpret the mechanism of action of such aging interventions, studies to characterize normal worm aging, similar to those used to study worm development are necessary. We have used 4′,6′‐diamidino‐2‐phenylindole hydrochloride staining and quantitative polymerase chain reaction to investigate the integrity of nuclei and quantify the nuclear genome copy number of C. elegans with age. We report both systematic loss of nuclei or nuclear DNA, as well as dramatic age‐related changes in nuclear genome copy number. These changes are delayed or attenuated in long‐lived daf‐2 mutants. We propose that these changes are important pathobiological characteristics of aging nematodes.
Pediatric Language Mapping: Sensitivity of Neurostimulation and Wada Testing in Epilepsy Surgery
Authors: Schevon Catherine A. , Carlson Chad , Zaroff Charles M. , Weiner Howard J. , Doyle Werner K. , Miles Daniel , Lajoie Josiane , Kuzniecky Ruben , Pacia Steven , Vazquez Blanca , Luciano Daniel , Najjar Souhel , Devinsky Orrin
Published: February 2007

Summary:  Purpose: Functional mapping of eloquent cortex with electrical neurostimulation is used both intra‐ and extraoperatively to tailor resections. In pediatric patients, however, functional mapping studies frequently fail to localize language. Wada testing has also been reported to be less sensitive in children.

Methods: Thirty children (4.7 – 14.9 years) and 18 adult controls (18–59 years) who underwent extraoperative language mapping via implanted subdural electrodes at the NYU Comprehensive Epilepsy Center were included in the study. Ten children and 14 adults underwent preoperative Wada testing. Success of the procedures was defined as the identification of at least one language site by neurostimulation mapping and determination of hemispheric language dominance on the Wada test.

Results: In children younger than 10.2 years, cortical stimulation identified language cortex at a lower rate than was seen in children older than 10.2 years and in adults (p < 0.05). This threshold, demonstrated by survival and χ2 analysis, was sharply defined in our data set. Additionally, Wada testing was more likely to be successful than was extraoperative mapping in this younger age group (p < 0.05).

Conclusions: Analysis of our series demonstrates that language cortex is less likely to be identified in children younger than 10 years, suggesting that alternatives to the current methods of cortical electrical stimulation, particularly the use of preoperative language lateralization, may be required in this age group.
Postoperative Recovery of Hippocampal Contralateral Diffusivity in Medial Temporal Lobe Epilepsy
Authors: Thivard Lionel , Tanguy Marie‐Laure , Adam Claude , Clémenceau Stéphane , Dezamis Edouard , Lehéricy Stéphane , Dormont Didier , Chiras Jacques , Baulac Michel , Dupont Sophie
Published: February 2007

Summary:  Purpose: To search for a recovery after surgery of mean diffusivity (MD) values in the contralateral nonsclerotic hippocampus of patients with medial temporal lobe epilepsy (MTLE) and hippocampal sclerosis (HS).

Methods: Twenty‐four MTLE patients (12 right‐sided and 12 left‐sided MTLE) and 36 healthy volunteers were investigated using diffusion tensor imaging. A region‐of‐interest approach was used to measure pre‐ and postoperative interictal hippocampal MD values in patients.

Results: Diffusion abnormalities in contralateral nonsclerotic hippocampus recovered after surgery (p < 0.0001). A subgroup of 14 patients exhibited a clear increase in MD values whereas the remaining 10 patients were stable. No significant difference was found between the two subgroups for each of the electroclinical data studied including early postoperative outcome, all patients being either seizure free or with rare persistent auras.

Conclusions: This finding suggests that diffusion abnormalities in contralateral hippocampus may represent a functional mechanism linked to the active epileptic process.
Only Male Mice Show Sensitization of Handling‐Induced Convulsions Across Repeated Ethanol Withdrawal Cycles
Authors: Veatch L.M. , Wright T.M. , Randall C.L.
Published: February 2007

Background: Alcohol abuse, especially when experienced in multiple cycles of chronic abuse and withdrawal, leads to a sensitization of central nervous system hyperexcitability that may culminate in overt expression of seizures. In spite of the growing prevalence of alcohol abuse and dependence in females shown in recent epidemiologic studies, evidence of sexual dimorphism in the expression of alcohol withdrawal‐induced seizures and the development of seizure sensitization following multiple cycles of ethanol (EtOH) exposure and withdrawal has not been examined in either animal models or in clinical reports.

Methods: Subjects in these experiments were male and female C3H/Hecr mice. The female mice were intact or ovariectomized, with ovariectomized mice receiving 17‐β‐estradiol or placebo pellets. All mice were exposed to 4 cycles of exposure to 16‐hour EtOH vapor, separated by 8‐hour withdrawal periods. During each 8‐hour withdrawal, hourly assessment of seizure propensity was assessed as handling‐induced convulsions. Additional assessments were taken up to 72 hours after the final EtOH withdrawal cycle.

Results: Male and female mice showed similar seizure propensity during an initial withdrawal from chronic EtOH. Across subsequent withdrawal cycles, however, male mice exhibited a robust increase in seizure severity beginning with the third withdrawal cycle. In marked contrast, female mice failed to demonstrate sensitization of seizure severity. The lack of seizure sensitization following up to 4 cycles of alcohol exposure and withdrawal could not be explained by hormonal status (presence or absence of estrogen) or by sex differences in blood alcohol levels.

Conclusions: Male and female mice exposed to the same number of cycles of EtOH withdrawal demonstrate differences in expression of seizures. Males show the typical sensitization of seizures, or kindling response, which has been reported clinically as well as in animal models, but females do not. The reason for the lack of seizure sensitization in female mice remains to be elucidated, but may be related to sex differences in alcohol effects on excitatory/inhibitory neurotransmission, rather than to hormonal or blood alcohol level differences.
Ear Acupuncture for Alcohol Withdrawal in Comparison With Aromatherapy: A Randomized‐Controlled Trial
Authors: Kunz Stephanie , Schulz Michael , Lewitzky Miriam , Driessen Martin , Rau Harald
Published: February 2007

Background: There is increasing clinical acceptance of acupuncture as a treatment of substance‐related disorders. Little is known about acupuncture as a treatment for the withdrawal syndrome in inpatient settings. We compared auricular needle acupuncture with aromatherapy in reducing the duration and severity of symptoms of alcohol withdrawal.

Methods: Inpatients undergoing alcohol withdrawal were randomly allocated to needle acupuncture (n=55) and aromatherapy (n=54). Both therapies were applied daily during the first 5 consecutive treatment days. The rating scale for the assessment of the alcohol‐withdrawal syndrome (AWS scale) served as the main dependent variable and was applied daily during the first 5 days of the withdrawal. Further measures included a subjective visual analog scale of craving and the Self Assessment Manikin (SAM).

Results: Thirty‐six of the 55 patients who received acupuncture, and 38 of the 54 patients who received aromatherapy, finished the study regularly. The groups differed in their initial self‐reported arousal, which then served as a covariate in the further analyses. Neither the extent of craving nor of withdrawal symptoms differed between groups over the observation period. Self‐rated arousal decreased in response to both treatments from days 1 to 2 (p<0.001) and within single days (p<0.001), and we found a significant interaction between pretreatment versus posttreatment and days (p<0.001). Interactions including between‐subjects effects and intervention did not achieve the significance level.

Conclusion: The results do not support the assumption of a superiority of acupuncture over the control therapy in its specific effects on alcohol withdrawal symptoms.
A Treatment Strategy for Psoriasis: Transitioning From Systemic Therapy to Biologic Agents
Authors: Ortiz Arisa , Yamauchi Paul S.
Published: February 2007

Systemic agents such as methotrexate and cyclo‐sporine are commonly used in the treatment of psoriasis. Long‐term continuous use is not recommended due to potential organ toxicity, myelosuppression, and carcinogenicity. Abrupt cessation of systemic agents without tapering can lead to flare‐up and rebound of psoriasis. The addition of a biologic agent during transitional therapy from a systemic agent is a good strategic maneuver to prevent a potential rebound complication. Even with a gradual cessation of systemic agents, the psoriasis will eventually relapse if biologic agents are not added to the treatment regimen. No additional toxicities or adverse events are evident during combination therapy with a systemic agent and a biologic agent.
Genetic and epigenetic analysis of the EPHB2 gene in gastric cancers
Authors: SONG JAE HWI , KIM CHANG JAE , CHO YONG GU , KWAK HYUN JUNG , NAM SUK WOO , YOO NAM JIN , LEE JUNG YOUNG , PARK WON SANG
Published: February 2007

EPHB2 is a member of the Eph receptor tyrosine kinase family and a direct transcriptional target of β‐catenin/TCF. EPHB2 plays an important role in maintaining the correct positioning of the proliferative compartment in the crypt‐villous axis. A loss of EPHB2 expression has been observed in human tumors, particularly in colonic adenomas and carcinomas. A search was made for mutations at the A9 tract in exon 17, an allelic loss at the EPHB2 gene locus, and promoter hypermethylation of the EPHB2 gene in 81 sporadic gastric cancers in order to determine if genetic or epigenetic alterations of the EPHB2 gene are involved in the development and/or progression of gastric cancer. Unexpectedly, no frameshift mutation was found and there was a low frequency (20.8%) of allelic loss. In addition, promoter hypermethylation was detected in only one gastric cancer tissue sample. Therefore, genetic or epigenetic alterations of the EPHB2 gene might be an uncommon event in the development or progression of gastric cancers.
Large cell neuroendocrine carcinoma of the ovary
Authors: LINDBOE C. F.
Published: February 2007

Large cell neuroendocrine carcinoma of the ovary is a recently described tumour entity that is now included in the WHO classification of primary ovarian neoplasms. Although mostly in stage I at diagnosis, this tumour shows an aggressive clinical behaviour with subsequent metastases and mean survival is less than one year. In addition to the neuroendocrine carcinoma, most cases also have a malignant surface epithelial tumour component. I here report a 64‐year‐old woman who was operated on for a right‐sided ovarian large cell neuroendocrine carcinoma without a surface epithelial component, which constitutes only the second reported tumour of this “pure” kind. Histological and immunohistochemical findings are described and a review of the literature is presented. The patient was treated postoperatively with chemotherapy. She developed bleomycin‐induced lung fibrosis that responded well to treatment with steroids. There have been no signs of local tumour recurrence or metastases at follow‐up examinations during the first 9 months after the operation.
Allergic contact dermatitis from methyldibromo glutaronitrile in a sanitary pad and review of Australian clinic data
Authors: Williams Jason D. , Frowen Kathryn E. , Nixon Rosemary L.
Published: February 2007

Methyldibromo glutaronitrile (MDBGN) has rarely been reported as an allergen in adhesives but is recognized as a common allergen in skin care products in Europe. It has been banned for use in leave‐on products by the European Union. In this study, we present a case with an unusual source of this common allergen and review all cases of allergy to MDBGN from our clinics over a 12‐year period. A 49‐year‐old nurse presented with dermatitis affecting the vulva caused by MDBGN present in her sanitary pad. All other cases of allergy to MDBGN in patients attending the occupational dermatology or contact dermatitis clinics at the Skin and Cancer Foundation, Victoria, between January 1993 and December 2004, were reviewed. Patch testing was positive to her sanitary pad, the adhesive and MDBGN, which were used as a biocide in the pad adhesive. Only 20 cases of allergy to MDBGN have been diagnosed in 2837 patients tested during this period (0.7%). To conclude, this study highlights the importance of considering allergic contact dermatitis in the differential diagnosis of vulval rashes and the emergence of MDBGN as an important sensitizer. However, our review suggests that MDBGN remains an infrequent cause of allergy in Australia.
LIVING THE QUESTIONS: RILKE’S CHALLENGE TO OUR QUEST FOR CERTAINTY
Authors: Gordon Mordechai
Published: February 2007

Abstract In this essay, Mordechai Gordon explores the significance of Rilke’s challenge to “live the questions” and embrace uncertainty with respect to the quest for certainty in education. The quest for certainty in education refers to our desire to gain a sense of psychological security and more control over a field that is fundamentally indeterminate. This quest implies an unwillingness to live with the inherent complexities and risks of education. After exploring the meaning and import of Rilke’s challenge and comparing it to the position of Socrates, Gordon uses Rilke’s insight to analyze a specific educational experience and then discusses some of its educational implications for teacher education.
Molecular basis for the subunit assembly of the primase from an archaeon Pyrococcus horikoshii
Authors: Ito Nobutoshi , Matsui Ikuo , Matsui Eriko
Published: February 2007

Archaeal/eukaryotic primases form a heterodimer consisting of a small catalytic subunit (PriS) and a large subunit (PriL). The heterodimer complex synthesizes primer oligoribonucleotides that are required for chromosomal replication. Here, we describe crystallographic and biochemical studies of the N‐terminal domain (NTD) of PriL (PriLNTD; residues 1–222) that bind to PriS from a hyperthermophilic archaeon, Pyrococcus horikoshii, at 2.9 Å resolution. The PriLNTD structure consists of two subdomains, the helix‐bundle and twisted‐strand domains. The latter is structurally flexible, and is expected to contain a PriS interaction site. Pull‐down and surface plasmon resonance analyses of structure‐based deletion and alanine scanning mutants showed that the conserved hydrophobic Tyr155‐Tyr156‐Ile157 region near the flexible region is the PriS‐binding site, as the Y155A/Y156A/I157A mutation markedly reduces PriS binding, by 1000‐fold. These findings and a structural comparison with a previously reported PriLNTD–PriS complex suggest that the presented alternative conformations of the twisted‐strand domain facilitate the heterodimer assembly.
Assessment of childhood allergy for the primary care practitioner
Authors: Dowdee April , Ossege Julie
Published: February 2007

Purpose: To update the primary care practitioner on the assessment of common childhood allergic illnesses.

Data sources: Relevant scientific literature and published clinical practice guidelines.

Conclusions: Atopic children often develop symptoms that occur in a predictable progression from atopic dermatitis to gastrointestinal disturbances, chronic serous otitis media, rhinitis, and asthma. Evaluation of allergic symptoms should be based on their chronicity, family history of atopy, and knowledge of how the information will change patient management. Both skin and blood testing are accurate and useful tools in establishing a diagnosis of allergic disease. Management includes avoidance/environmental control, medications, and, when necessary, referral to specialists.

Implications for practice: As the incidence of allergic disease increases, the human and monetary costs associated with allergies place a major burden on our healthcare system. Early identification of allergies and appropriate intervention are important to prevent progression to more significant disease. The use of objective diagnostic testing aids in implementing appropriate evidence‐based medical management.
THE EFFICIENCY‐STABILITY TRADE‐OFF: THE CASE OF HIGH INTEREST RATE SPREADS IN VENEZUELA
Authors: VERA Leonardo , ZAMBRANO‐SEQUÍN Luis , FAUST Andreas
Published: February 2007

This paper examines the determinants of the high intermediation spread observed in the Venezuelan banking sector during the 1990s (by far the largest in the Latin American region throughout the 1990s). We trace the evolution of the spread and its connection with other bank‐specific variables. A reduced‐form equation is estimated on the basis of a simple behavioral model for the banking firm previously developed by Shaffer and extended by Barajas, Steiner, and Salazar. Using different types of estimators for aggregate and pooled data of the financial system, we found that high spreads can be attributed to market power, high operating costs, and expected portfolio risk. The empirical results also suggest a trade‐off between assuring bank solvency and lowering profitability.
Syndactyly in a litter of cats
Authors: Towle H. A. , Blevins W. E. , Tuer L. R. , Breur G. J.
Published: February 2007

In this case report, we describe the clinical and radiographic features of a litter of kittens affected with complex syndactyly. We also provide guidelines for the diagnosis, possible treatment and prevention of propagation of this condition. This is the first report of syndactyly in a litter of kittens and syndactyly affecting both the pectoral and pelvic limbs.
Transcatheter embolisation of patent ductus arteriosus using an Amplatzer vascular plug in six dogs
Authors: Smith P. J. , Martin M. W. S.
Published: February 2007

Objectives:The objective of this study was to assess the feasibility of transcatheter embolisation of a patent ductus arteriosus using an Amplatzer vascular plug (Amplatzer Medical UK) in six dogs.

Methods:The Amplatzer vascular plug is a self‐expandable, cylindrical device attached to a delivery cable. In all the dogs, the device was delivered transvenously. Successful device implantation was defined as firm anchorage of the device squarely within the distal part of the ductus arteriosus with no intra‐ or postoperative dislodgement. Successful occlusion of the ductus arteriosus occurred if a disappearance of the continuous murmur was achieved 24 hours after placement of the Amplatzer vascular plug.

Results:The age of the dogs ranged from 16 weeks to 7·5 years. Their weights ranged from 2·9 to 27·6 kg (median 6 kg). Two dogs had congestive heart failure before embolisation. Successful device implantation was achieved in all dogs. Successful occlusion of the ductus arteriosus was achieved in four of the six dogs. Complications included mild lameness, residual shunting, and bruising and pruritus around the surgical wound site. At follow‐up, two dogs had a continuous murmur and one required treatment for congestive heart failure.

ClinicalSignificance:This technique may represent a clinically effective and less expensive alternative to the use of an Amplatzer duct occluder (Amplatzer Medical UK) in dogs with medium‐sized patent ductus arteriosus. Further investigations are required to fully evaluate its efficacy and safety in various sizes and types of patent ductus arteriosus, and to determine the optimal device size in relation to the size of the ductus.