bluuebunny/crossref_metadata_2025 huggingface dataset:
Avian blood parasites in an endangered columbid:Leucocytozoon marchouxiin the Mauritian Pink PigeonColumba mayeri
Authors: BUNBURY N. , BARTON E. , JONES C. G. , GREENWOOD A. G. , TYLER K. M. , BELL D. J.
Published: January 2007

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 PigeonColumba 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. marchouxiinfection 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 withL. marchouxiwas 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.
O brother, let's go down home: loss, nostalgia and the blues
Authors: MIDDLETON RICHARD
Published: January 2007

The blues genre is commonly (and not incorrectly) regarded as a key marker of African-American identity and one with ‘deep’ (folk, or ‘down home’) roots. But this status is inadequately understood unless it is placed in a context of inter-racial exchange, in which ‘roots’ are a product of a complex transaction between ‘modernity’ and ‘tradition’. This territory is explored in terms of a thematics of loss, nostalgia and trauma, evident both in blues content and in the historical structure of revival to which the genre has been continually subject. A useful background is the film O Brother, Where Art Thou?, a nostalgic celebration of nostalgia with a blues/bluegrass inter-racial dimension, and a productive theoretical framework is provided by Lacan's approach to fantasy, loss and nostalgia.
From Negative to Positive Equality Duties: The Development and Constitutionalisation of Equality Provisions in the UK
Authors: McLaughlin Eithne
Published: January 2007

This paper reviews the development and nature of one of the two components of the UK's equality regime – equality law. The origins of equality law lie in the postwar consensus on non-discrimination. The paper reviews the limitations of non-discrimination or negative equality duties. It documents the expansion of equality law at the turn of the twentieth/twenty-first century, when seven UK Acts and two European Directives introduced additional negative equality duties, provided for a new enforcement authority and introduced positive equality duties in respect of some social statuses. Many of these duties were introduced as part of devolution arrangements. UK equality law leads the field in European terms. The nature of positive equality duties and New Labour's approach to equality in general are also critiqued.
Using Statistical Analysis for Setting Process Validation Acceptance Criteria for Biotech Products
Authors: Wang Xiangyang , Germansderfer Abe , Harms Jean , Rathore Anurag S.
Published: January 2007

This paper discusses the challenges of setting process validation acceptance criteria for biotech products for cases where using statistical tools is appropriate. Data are analyzed under three different scenarios that are frequently encountered in biotech applications. Scenario A represents the case when a small data set around center point conditions is available for setting acceptance criteria. Scenario B represents the case when a larger data set within normal operation conditions is available for setting acceptance criteria. Scenario C represents the case when a large characterization data set is available for setting acceptance criteria and it is possible to accurately model the impact of operation conditions on performance of the step. Statistical approaches including mean ± 3SD, tolerance interval analysis, prediction profiler, and Monte Carlo simulation are applied to the different scenarios. Strengths and shortcomings of the different statistical tools are discussed, and the best approach for each scenario is recommended. It is shown that selection of the right statistical approach is a critical first step toward setting appropriate acceptance criteria.
Application of Multivariate Analysis toward Biotech Processes: Case Study of a Cell‐Culture Unit Operation
Authors: Kirdar Alime Ozlem , Conner Jeremy S. , Baclaski Jeffrey , Rathore Anurag S.
Published: January 2007

This paper examines the feasibility of using multivariate data analysis (MVDA) for supporting some of the key activities that are required for successful manufacturing of biopharmaceutical products. These activities include scale‐up, process comparability, process characterization, and fault diagnosis. Multivariate data analysis and modeling were performed using representative data from small‐scale (2 L) and large‐scale (2000 L) batches of a cell‐culture process. Several input parameters (pCO2, pO2, glucose, pH, lactate, ammonium ions) and output parameters (purity, viable cell density, viability, osmolality) were evaluated in this analysis. Score plots, loadings plots, and VIP plots were utilized for assessing scale‐up and comparability of the cell‐culture process. Batch control charts were found to be useful for fault diagnosis during routine manufacturing. Finally, observations made from reviewing VIP plots were found to be in agreement with conclusions from process characterization studies demonstrating the effectiveness of MVDA as a tool for extracting process knowledge.
Influence of the mineralogical composition on the self‐potential response to advection of KCl concentration fronts through sand
Authors: Maineult Alexis , Jouniaux Laurence , Bernabé Yves
Published: January 2007

We measured the self‐potential (SP) response to advective transport of KCl concentration fronts through two laboratory‐scale sand‐bodies with different mineralogical composition. In pure quartz sand, the amplitude and polarity of the SP signals agreed with a previously published model. In sand containing 3% potassic feldspars and 1% micas and clays, the shape of the SP response differed significantly: the amplitude was much larger than the model prediction and a change in polarity occurred after the passage of the front. Furthermore, the KCl concentration in the effluent was strongly reduced. We suggest that the minor mineral phases reacted with the K+ ions, trapping them during the front passage and releasing them later. Even though the reactions involved are not fully identified to date, this study demonstrates that even small amounts of chemically active mineral phases, such as micas or clays, can significantly influence the SP signals.
Simultaneous inversion of active and passive source datasets for 3‐D seismic structure with application to Tasmania
Authors: Rawlinson N. , Urvoy M.
Published: January 2007

Refraction, wide‐angle reflection and teleseismic arrival time data are combined in a simultaneous inversion for 3‐D lithospheric P‐wavespeed and Moho geometry beneath Tasmania, southeast Australia. A new iterative non‐linear tomography scheme, which incorporates a novel grid‐based method of traveltime prediction, is used to obtain the solution model. Synthetic resolution tests demonstrate that the crucial issue of trade‐off between interface depth and layer velocity is satisfactorily resolved. In contrast to previous results from separate inversions of the active and passive source datasets, the new images reveal a zone of elevated wavespeed beneath the Cambrian Mt. Read Volcanics, and indicate that both crustal thinning and elevated wavespeeds occur beneath northeast Tasmania, which supports the case for the existence of a prior passive margin. Otherwise, most major inferences from the previous studies, including evidence for remnant subduction and crustal shortening, are supported by the new results.
Modulation of drug-stimulated ATPase activity of human MDR1/P-glycoprotein by cholesterol
Authors: Kimura Yasuhisa , Kioka Noriyuki , Kato Hiroaki , Matsuo Michinori , Ueda Kazumitsu
Published: January 2007

MDR1 (multidrug resistance 1)/P-glycoprotein is an ATP-driven transporter which excretes a wide variety of structurally unrelated hydrophobic compounds from cells. It is suggested that drugs bind to MDR1 directly from the lipid bilayer and that cholesterol in the bilayer also interacts with MDR1. However, the effects of cholesterol on drug–MDR1 interactions are still unclear. To examine these effects, human MDR1 was expressed in insect cells and purified. The purified MDR1 protein was reconstituted in proteoliposomes containing various concentrations of cholesterol and enzymatic parameters of drug-stimulated ATPase were compared. Cholesterol directly binds to purified MDR1 in a detergent soluble form and the effects of cholesterol on drug-stimulated ATPase activity differ from one drug to another. The effects of cholesterol on Km values of drug-stimulated ATPase activity were strongly correlated with the molecular mass of that drug. Cholesterol increases the binding affinity of small drugs (molecular mass <500 Da), but does not affect that of drugs with a molecular mass of between 800 and 900 Da, and suppresses that of valinomycin (molecular mass >1000 Da). Vmax values for rhodamine B and paclitaxel are also increased by cholesterol, suggesting that cholesterol affects turnover as well as drug binding. Paclitaxel-stimulated ATPase activity of MDR1 is enhanced in the presence of stigmasterol, sitosterol and campesterol, as well as cholesterol, but not ergosterol. These results suggest that the drug-binding site of MDR1 may best fit drugs with a molecular mass of between 800 and 900 Da, and that cholesterol may support the recognition of smaller drugs by adjusting the drug-binding site and play an important role in the function of MDR1.
Two metallocarboxypeptidases from the protozoan Trypanosoma cruzi belong to the M32 family, found so far only in prokaryotes
Authors: Niemirowicz Gabriela , Parussini Fabiola , Agüero Fernán , Cazzulo Juan J.
Published: January 2007

MCPs (metallocarboxypeptidases) of the M32 family of peptidases have been identified in a number of prokaryotic organisms, and only a few of them have been characterized biochemically. Members of this family are absent from eukaryotic genomes, with the remarkable exception of those of trypanosomatids. The genome of the CL Brener clone of Trypanosoma cruzi, the causative agent of Chagas' disease, encodes two such MCPs, with 64% identity between them: TcMCP-1 and TcMCP-2. Both genes, which are present in a single copy per haploid genome, were expressed in Escherichia coli as catalytically active polyHis-tagged recombinant enzymes. Despite their identity, the purified TcMCPs displayed marked biochemical differences. TcMCP-1 acted optimally at pH 6.2 on FA {N-(3-[2-furyl]acryloyl)}-Ala-Lys with a Km of 166 μM. Activity against benzyloxycarbonyl-Ala-Xaa substrates revealed a P1′ preference for basic C-terminal residues. In contrast, TcMCP-2 preferred aromatic and aliphatic residues at this position. The Km value for FA-Phe-Phe at pH 7.6 was 24 μM. Therefore the specificities of both MCPs are complementary. Western blot analysis revealed a different pattern of expression for both enzymes: whereas TcMCP-1 is present in all life cycle stages of T. cruzi, TcMCP-2 is mainly expressed in the stages that occur in the invertebrate host. Indirect immunofluorescence experiments suggest that both proteins are localized in the parasite cytosol. Members of this family have been identified in other trypanosomatids, which so far are the only group of eukaryotes encoding M32 MCPs. This fact makes these enzymes an attractive potential target for drug development against these organisms.
The regulation of ATF3 gene expression by mitogen-activated protein kinases
Authors: Lu Dan , Chen Jingchun , Hai Tsonwin
Published: January 2007

ATF3 (activating transcription factor 3) gene encodes a member of the ATF/CREB (cAMP-response-element-binding protein) family of transcription factors. Its expression is induced by a wide range of signals, including stress signals and signals that promote cell proliferation and motility. Thus the ATF3 gene can be characterized as an ‘adaptive response’ gene for the cells to cope with extra- and/or intra-cellular changes. In the present study, we demonstrate that the p38 signalling pathway is involved in the induction of ATF3 by stress signals. Ectopic expression of CA (constitutively active) MKK6 [MAPK (mitogen-activated protein kinase) kinase 6], a kinase upstream of p38, indicated that activation of the p38 pathway is sufficient to induce the expression of the ATF3 gene. Inhibition of the pathway indicated that the p38 pathway is necessary for various signals to induce ATF3, including anisomycin, IL-1β (interleukin 1β), TNFα (tumour necrosis factor α) and H2O2. Analysis of the endogenous ATF3 gene indicates that the regulation is at least in part at the transcription level. Specifically, CREB, a transcription factor known to be phosphorylated by p38, plays a role in this induction. Interestingly, the ERK (extracellular-signal-regulated kinase) and JNK (c-Jun N-terminal kinase)/SAPK (stress-activated protein kinase) signalling pathways are neither necessary nor sufficient to induce ATF3 in the anisomycin stress paradigm. Furthermore, analysis of caspase 3 activation indicated that knocking down ATF3 reduced the ability of MKK6(CA) to exert its pro-apoptotic effect. Taken together, our results indicate that a major signalling pathway, the p38 pathway, plays a critical role in the induction of ATF3 by stress signals, and that ATF3 is functionally important to mediate the pro-apoptotic effects of p38.
Unusual phyletic distribution of peptidases as a tool for identifying potential drug targets
Authors: Rawlings Neil D.
Published: January 2007

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.
Elastic response of a nematic liquid crystal to an immersed nanowire
Authors: Smith Christopher J. , Denniston Colin
Published: January 2007

We study the immersion of a ferromagnetic nanowire within a nematic liquid crystal using a lattice Boltzmann algorithm to solve the full three-dimensional equations of hydrodynamics. We present an algorithm for including a moving boundary, to simulate a nanowire, in a lattice Boltzmann simulation. The nematic imposes a torque on a wire that increases linearly with the angle between the wire and the equilibrium direction of the director field. By rotation of these nanowires, one can determine the elastic constants of the nematic.
Characteristics of coplanar waveguide on lithium niobate crystals as a microwave substrate
Authors: Yang Ru-Yuan , Su Yan-Kuin , Weng Min-Hang , Hung Cheng-Yuan , Wu Hung-Wei
Published: January 2007

A finite ground coplanar waveguide (FG-CPW) on lithium niobate (LiNbO3) substrates, without a thin SiO2 buffer layer, was experimentally characterized by using on-wafer measurements. The dielectric constant and the characteristic impedance were extracted from calibrated measurements made at up to 20GHz using the FG-CPW method. The loss tangent was then obtained by the conformal mapping approach after the dielectric constant and characteristic impedance had been accurately extracted. The dielectric losses of LiNbO3 substrates are not negligible even in the X band.
Transmission properties of nanoscale aperture arrays in metallic masks on optical fibers
Authors: Tian L. , Frisbie S. , Bernussi A. A. , Holtz M.
Published: January 2007

We report the optical studies of nanohole arrays in metallic coatings on cleaved optical fibers and also on glass substrates. Nanoholes are produced using electron-beam lithography and range in size from 100to700nm; the pitch is varied from 300to3000nm. Transmission properties are examined using visible (632.8nm) and infrared (1550nm) laser light. The observed interference patterns are determined by array symmetry, nanohole diameter, and pitch. Results from the optical fibers are compared with larger array areas fabricated on bulk glass substrates. In all cases the results are simulated using near- and intermediate-field diffraction theory with good agreement.
Effect of Ta getter on the quality of MgO tunnel barrier in the polycrystalline CoFeB∕MgO∕CoFeB magnetic tunnel junction
Authors: Choi Y. S. , Nagamine Y. , Tsunekawa K. , Maehara H. , Djayaprawira D. D. , Yuasa S. , Ando K.
Published: January 2007

X-ray photoelectron spectroscopy and high-resolution Rutherford backscattering reveal that Ta getter presputtering enhances the stoichiometry and lowers the interstitial defect density of MgO barrier. This results in higher magnetoresistance ratio, 205%, of magnetic tunnel junction, compared to 46% for no Ta getter, at 1.2nm MgO thickness. Fitting yields the corresponding barrier height of the MgO of 3.0eV, which is higher compared to 2.3eV for without Ta getter. However, the tunnel junction prepared with Ta getter shows lower resistance-area product by an order of magnitude. Microstructure of MgO barrier and oxidation of bottom electrode can be attributed to the contradictory results.
Diarylethene microcrystals make directional jumps upon ultraviolet irradiation
Authors: Colombier I. , Spagnoli S. , Corval A. , Baldeck P. L. , Giraud M. , Leaustic A. , Yu P. , Irie M.
Published: January 2007

Microcrystals of a diarylethene {1,2-bis[5′-methyl-2′-(2″-pyridyl)thiazolyl]perfluorocyclo-pentene} undergo jumps upon photoirradiation. These photochromic crystals present molecular structural changes upon irradiation with ultraviolet light because of reversible photocyclization reactions. When the energy absorbed by crystals reaches about 10μJ, the uniaxial stress induced in the crystal lattice relaxes through directional jumps. If one prevents crystals from jumping, then parallel, equidistant cracks appear on crystal surfaces. These photomechanical effects could result from a Grinfeld surface instability.
Crystal structure of the C-terminal domain of Ebola virus VP30 reveals a role in transcription and nucleocapsid association
Authors: Hartlieb Bettina , Muziol Tadeusz , Weissenhorn Winfried , Becker Stephan
Published: January 2007

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-Å 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.
MAPK regulation of maternal and zygotic Notch transcript stability in early development
Authors: Gonsalves Foster C. , Weisblat David A.
Published: January 2007

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.
Neural substrates of envisioning the future
Authors: Szpunar Karl K. , Watson Jason M. , McDermott Kathleen B.
Published: January 2007

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.
Eukaryotic ternary transcription complexes: transcription complexes of RNA polymerase II are associated with histone-containing, nucleosome-like particles in vivo
Authors: Sargan David R. , Butterworth Peter H.W.
Published: January 2007

Using a psoralen crosslinking, radioactive labelling technique, we have previously been able to study ternary transcription complexes containing DNA-dependent RNA polymerases I and II which are released from rat liver nuclei by endogenous nuclease digestion [Sargan and Butterworth, refs 1 and 2]. Although the DNA component of these complexes was found to have a ‘nucleosome-Uke’ size profile and although the experimental conditions for autodigestion were designed to minimise histone rearrangement, 1t is necessary to provide further evidence that the periodicity of nuclease cutting around these transcription complexes 1s conferred by histones. Studies using secondary nuclease digestion of the released transcription complexes now show a digestion barrier characteristic of that conferred by nucleosomal histones which is lost if histones are removed from the complexes. Furthermore, antibodies raised against histones are effective in precipitating transcription complexes of RNA polymerase II and, to a lesser extent, of RNA polymerase I. The data suggest that, in rat hepatic tissue, transcription complexes are in very close proximity (within a few hundred base pairs) of histone-containing, nucleosome-like particles in vivo
Fidelity of DNA synthesis by the Thermococcus litoralis DNA polymerase—an extremely heat stable enzyme with proofreading activity
Authors: Mattila P. , Korpela J. , Tenkanen T. , Pitkämem K.
Published: January 2007

We demonstrate that the DNA polymerase isolated from Thermococcus litoralis (VentTM DNA polymerase) is the first thermostable DNA polymerase reported having a 3′—5′ proofreading exonuclease activity. This facilitates a highly accurate DNA synthesis in vitro by the polymerase. Mutational frequencies observed in the base substitution fidelity assays were in the range of 30×10−6. These values were 5–10 times lower compared to other thermostable DNA polymerases lacking the proofreading activity. All classes of DNA polymerase errors (transitions, transversions, frameshift mutations) were assayed using the forward mutational assay (1). The mutation frequencies of Thermococcus litoralis DNA polymerase varied between 15−35×10−4 being 2 – 4 times lower than the respective values obtained using enzymes without proofreading activity. We also noticed that the fidelity of the DNA polymerase from Thermococcus litoralis responds to changes in dNTP concentration, units of enzyme used per one reaction and the concentration of MgSO4 relative to the total concentration of dNTPs present in the reaction. The high fidelity DNA synthesis In vitro by Thermococcus litoralis DNA polymerase provides good possibilities for maintaining the genetic information of original target DNA sequences intact in the DNA amplification applications.
Surfactant Protein D Expression in Chronic Rhinosinusitis Patients and Immune Responses In Vitro to Aspergillus and Alternaria in a Nasal Explant Model
Authors: Ooi Eng Hooi , Wormald Peter‐John , Carney A Simon , James Craig Lloyd , Tan Lor Wai
Published: January 2007

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.
Sialoendoscopic Treatment for Radioiodine Induced Sialadenitis
Authors: Kim Jae Won , Han Gil Soo , Lee Seung Ho , Lee Dong Yul , Kim Young‐Mo
Published: January 2007

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.
Operating Room Versus Office‐Based Injection Laryngoplasty: A Comparative Analysis of Reimbursement
Authors: Bové Michiel J. , Jabbour Noel , Krishna Priya , Flaherty Kathi , Saul Melissa , Wunar Robert , Rosen Clark A.
Published: January 2007

Background: Injection laryngoplasty (IL) continues to evolve as new indications, techniques, approaches, and injection materials are developed. Although historically performed under local or general anesthesia in the operating room suite, IL is now increasingly being performed in an office‐based setting. This report presents the results of a reimbursement analysis comparing office‐based versus operative IL.

Objective: The objective of this study was to compare the reimbursement of office‐based injection laryngoplasty with the reimbursement of performing the same procedure in the operating room.

Design: The authors conducted reimbursement and outcome analysis through retrospective office chart and hospital record review.

Methods: A retrospective review was performed of the hospital records of patients having undergone injection laryngoplasty at the University of Pittsburgh Voice Center from July 1998 through March 2005. Group I included patients who underwent IL in the operating room, whereas group II included those who had office‐based IL. A reimbursement analysis for both groups was then performed comparing surgeon fees, anesthesia, and hospital charges and reimbursement. The clinical efficacy of IL performed in either office versus operating room settings was measured by comparing the pre‐ and postintervention Voice Handicap Index‐10 scores for all patients. A predictive model of potential cost savings is developed based on the results of the analysis.

Results: Average reimbursement was $2,505 for group I (n = 108) and $496 for group II (n = 50). This reimbursement differential was preserved across the various insurance types examined. There was no significant difference in Voice Handicap Index‐10 change after surgery between group I and II.

Conclusions: Office‐based IL is both clinically and financially effective, providing patients with a convenient and flexible alternative to operating room‐based intervention for glottal insufficiency.
Extraction of the Plasticizers Diethylhexylphthalate and Polyadipate From Polyvinylchloride Nasogastric Tubes Through Gastric Juice and Feeding Solution
Authors: Subotic Ulrike , Hannmann Torsten , Kiss Matthias , Brade Joachim , Breitkopf Katja , Loff Steffan
Published: January 2007

Objectives:

Except for polyadipate, which is used as an alternative in polyvinylchloride (PVC) feeding tubes, diethylhexylphthalate (DEHP) is the plasticizer used almost exclusively in PVC medical products. A clear response to the chronic intake of DEHP has been shown in several organ systems from different species. In the present study, we compared the extraction of DEHP and polyadipate from PVC gastric tubes.

Methods:

An in vivo setting was simulated. We used 5 cm of PVC nasogastric tubes containing DEHP or polyadipate, which were incubated with gastric juice for 1 week and a feeding solution for 4 weeks. The leakage of these plasticizers was measured daily in the gastric juice group and weekly in the feeding solution group. The amount of plasticizer extracted was compared between groups and days.

Results:

In the feeding solution group, the extraction of DEHP ranged from 200 to 542 μg after 1 week and from 660 to 1700 μg after 4 weeks. The extraction of polyadipate was 10 times lower than that of DEHP. In the gastric juice group, extracted DEHP ranged from 635 to 1043 μg, whereas the extraction of polyadipate was 100 times lower.

Conclusions:

Within 1 week, the extraction of DEHP from a 5‐cm PVC tube reaches up to 1 mg. Extrapolated, this represents an in vivo load of up to 4 mg. The load accumulated by a newborn in an intensive care unit can therefore easily reach several milligrams of DEHP per day. Polyadipate nasogastric tubes may therefore be an alternative and help to reduce the daily load of DEHP.
Enriching the environment of αCaMKIIT286A mutant mice reveals that LTD occurs in memory processing but must be subsequently reversed by LTP
Authors: Parsley Stephanie L. , Pilgram Sara M. , Soto Florentina , Giese K. Peter , Edwards Frances A.
Published: January 2007

αCaMKIIT286A 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 αCaMKII 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 αCaMKIIT286A 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 αCaMKII-independent changes in both wild-type and mutant mice. Such changes may be subsequently reversed in wild-type animals via αCaMKII-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 αCaMKIIT286A mutant mice would then result in impairment of spatial learning.
Quality of life and psychological morbidity in women with polycystic ovary syndrome: body mass index, age and the provision of patient information are significant modifiers
Authors: Ching H. L. , Burke V. , Stuckey B. G. A.
Published: January 2007

Objective  Polycystic ovary syndrome (PCOS) has clinical features and implications for long‐term health that may lead to decreased quality of life (QoL) and psychological morbidity. We studied QoL in women with PCOS, compared the findings with population norms and assessed whether they correlated with reported quality of patient information received.

Design  Cross‐sectional study.

Patients  Women with PCOS by National Institutes of Health (NIH) criteria, diagnosis confirmed by one endocrinologist.

Measurements  Four questionnaires were mailed: the Short Form‐36 (SF‐36), the Quality‐of‐Life Questionnaire for Women with Polycystic Ovary Syndrome (PCOSQ), the General Health Questionnaire‐28 (GHQ‐28) and an assessment of information quality and sources, the Patient Information Questionnaire (PIQ).

Results  Questionnaires were sent to 443 women with PCOS from one endocrinologist's database; 203 women aged 15–65 years agreed to participate. To compare with Australian population norms, data from those women aged 18–44 years (n = 173) were used. Of these, 64% were obese, 18% overweight and 18% of normal weight. The demographics, socioeconomic status and untreated biochemistry of the responders and the total patient group were not significantly different. SF‐36 scores were significantly lower than the age‐ and sex‐matched Australian population (P < 0·01), including the overweight subset (P < 0·01). Health‐related QoL by PCOSQ was similar to other published studies. GHQ‐28 identified psychological morbidity in 62·4%, compared with 26·4% in a matched Australian population (P < 0·0001). Body mass index (BMI) was negatively correlated with QoL (P < 0·01). There was a positive association between the psychological domain of QoL and the subjective assessment of the quality of health‐related information in general (P < 0·001), for hirsutism (P < 0·01) and for menstrual irregularity (P < 0·05).

Conclusions  We have shown impaired QoL and increased prevalence of psychological morbidity in PCOS compared with population norms. The perception of inadequate information about the condition correlated with poorer QoL scores. Improved information delivery may lead to an improvement in QoL and needs to be tested with an intervention study.
Implications of resistin plasma levels in subjects undergoing coronary angiography
Authors: Pilz Stefan , Weihrauch Gisela , Seelhorst Ursula , Wellnitz Britta , Winkelmann Bernhard R. , Boehm Bernhard O. , März Winfried
Published: January 2007

Background  The adipokine resistin, which is thought to serve as a link between obesity and insulin resistance, was recently shown to exert proatherosclerotic features.

Objective  Our study aimed to explore the involvement of resistin in cardiovascular disease by investigating the associations of resistin with angiographic coronary artery disease (CAD), cardiovascular risk factors and mortality.

Design  The Ludwigshafen Risk and Cardiovascular Health (LURIC) study is a prospective study of white subjects who had undergone coronary angiography.

Patients and measurements  Resistin levels were determined in 1162 subjects with (n = 911) and without (n = 251) angiographic CAD. During a mean follow‐up period of 5·47 years, 198 deaths occurred among our probands.

Results  Resistin was positively correlated with C‐reactive protein (CRP; r = 0·245, P < 0·001), vascular adhesion molecule‐1 (VCAM‐1; r = 0·327, P < 0·001) and intercellular adhesion molecule‐1 (ICAM‐1; r = 0·197, P < 0·001) and was negatively correlated with glomerular filtration rate (GFR; r = –0·438, P < 0·001) and high density lipoprotein (HDL; r = –0·196, P < 0·001). Multiple regression analysis revealed that GFR was the strongest predictive variable for resistin. Angiographic CAD, type 2 diabetes, smoking, hypertension and body mass index (BMI) were not associated with resistin. Compared to the first quartile, we observed an increased risk for cardiovascular and noncardiovascular mortality at the fourth quartile of resistin, but only the association between resistin and noncardiovascular mortality remained significant after multivariable adjustments [hazard ratio (HR) 4·92, 95% confidence interval (CI) 1·66–14·6, P = 0·004].

Conclusions  Resistin plasma concentrations are related to inflammatory processes and renal function but our study does not support the hypothesis of resistin as an independent cardiovascular risk factor. The unexpected association of resistin with noncardiovascular mortality still warrants further study.
Interstitial cells of Cajal in health and disease. Part II: ICC and gastrointestinal stromal tumours
Authors: Streutker C J , Huizinga J D , Driman D K , Riddell R H
Published: January 2007

Mesenchymal tumours in the gastrointestinal tract have long been problematic in terms of diagnosis, prognosis and therapy, but recent advances in immuohistochemistry and related therapies have allowed more specific diagnosis. In particular, the recognition that both the interstitial cells of Cajal (ICC) and many gastrointestinal stromal tumours (GISTs) are positive for c‐kit and CD34 and have other features similar to those of ICC has led to the use of imatinib, a novel small molecule therapy that blocks the CD117/c‐kit tyrosine kinase receptor, which shows remarkable efficacy in treatment of malignant and metastatic GISTs as well as other malignancies.
Organizing pneumonia and lymphoplasmacytic inflammation predict treatment response in idiopathic pulmonary fibrosis
Authors: Collard H R , Cool C D , Leslie K O , Curran‐Everett D , Groshong S , Brown K K
Published: January 2007

Aims:  To identify individual histopathological features within usual interstitial pneumonia pattern that predict responsiveness to immunosuppressive therapy.

Methods and results:  Fifty‐six retrospectively confirmed usual interstitial pneumonia pattern surgical lung biopsy specimens from subjects with idiopathic pulmonary fibrosis treated with corticosteroid and cytotoxic therapy were included. Eleven prospectively defined histopathological features were evaluated by two expert pulmonary pathologists. Regression analysis identified predictors of response to therapy, as defined by the change in percent predicted forced vital capacity over 6 months. Additional end‐points were change in dyspnoea score over 6 months, and survival time. Improvement in percent predicted forced vital capacity was associated with lymphoplasmacytic inflammation, while worsening of percent predicted forced vital capacity was associated with the presence of organizing pneumonia and fibroblast foci. Worsening dyspnoea was associated with fibroblast foci. Survival time was associated with age and baseline percent predicted forced vital capacity, but not with any individual histopathological feature.

Conclusions:  In pathological usual interstitial pneumonia pattern, the presence of lymphoplasmacytic inflammation predicts responsiveness to immunomodulatory therapy, while airspace organization predicts lack of response.
Heterogeneous expression of α‐methylacyl‐CoA racemase in prostatic cancer correlates with Gleason score
Authors: Murphy A J , Hughes C A , Lannigan G , Sheils O , O'Leary J , Loftus B
Published: January 2007

Aims:  α‐Methylacyl‐CoA racemase (AMACR) is a sensitive and specific immunohistochemical marker of prostatic malignancy, staining 80–100% of prostatic cancers with absent staining in benign glands. However, positive staining in benign conditions as well as low rates of AMACR reactivity in prostatic cancer variants have been described. Preliminary use of AMACR immunohistochemistry in our institution has suggested lower specificity and sensitivity for prostatic cancer than initially proposed. The aim of this study was to establish true rates of AMACR reactivity in prostatic cancer and benign prostatic hyperplasia (BPH).

Methods and results:  AMACR immunohistochemistry was performed on sections from 57 prostatic cancers and 44 BPH resections. Ninety‐one percent of cancers were AMACR+, with diffuse (> 75%) tumour staining in 53% of cases. Thirty‐eight percent of tumours showed heterogeneous expression (1–75% tumour staining). This was significantly correlated with increased Gleason score. High‐grade prostatic intraepithelial neoplasia (PIN) was AMACR+ in 87% of cancers. Eleven percent of BPH showed moderate or strong staining in benign glands, focally mimicking the malignant staining pattern.

Conclusions:  This study confirms heterogeneous AMACR expression in prostatic cancer and shows a correlation with Gleason score. Positive staining in BPH is also documented, thus emphasizing the importance of interpreting AMACR immunohistochemistry in the context of other findings in a diagnostic setting.
Evidence for airway surface dehydration as the initiating event in CF airway disease
Authors: Boucher R. C.
Published: January 2007

Cystic fibrosis (CF) lung disease reflects persistent bacterial infection of airway lumens. Several hypotheses have been advanced to link mutations in the CFTR gene to the failure of the CF lung to defend itself against bacterial infection. Amongst the most productive hypotheses at present is the ‘‘low airway surface liquid (ASL) volume’’ or ‘‘dehydration’’ hypothesis. This hypothesis predicts that airway surface dehydration produces the mucus adhesion, inflammation, and bacterial biofilm formation characteristic of CF. Clinical trials of inhaled hypertonic saline have demonstrated therapeutic benefit of manoeuvres designed to rehydrate CF airway surfaces.
Regulation and dysregulation of aquaporins in water balance disorders*
Authors: Nielsen S. , Kwon T.‐H. , Frøkiær J. , Agre P.
Published: January 2007

The discovery of aquaporin‐1 (AQP1) explained the long‐standing biophysical question of how water specifically crosses biological membranes. These studies led to the identification of a whole new family of membrane proteins, the aquaporin water channels. At present, at least eight aquaporins are expressed at distinct sites in the kidney and four members of this family (AQP1‐4) have been demonstrated to play pivotal roles in the physiology and pathophysiology for renal regulation of body water balance. In the present review, a number of inherited and acquired conditions characterized by urinary concentration defects as well as common diseases associated with severe water retention are discussed with relation to the role of aquaporins in regulation and dysregulation of renal water transport.