bluuebunny/crossref_metadata_2025 huggingface dataset:
Psoriasin, one of several new proteins identified in nasal lavage fluid from allergic and non-allergic individuals using 2-dimensional gel electrophoresis and mass spectrometry
Authors: Bryborn Malin , Adner Mikael , Cardell Lars-Olaf
Published: October 2005

Background

Extravasation and luminal entry of plasma occurs continuously in the nose. This process is markedly facilitated in patients with symptomatic allergic rhinitis, resulting in an increased secretion of proteins. Identification of these proteins is an important step in the understanding of the pathological mechanisms in allergic diseases. DNA microarrays have recently made it possible to compare mRNA profiles of lavage fluids from healthy and diseased patients, whereas information on the protein level is still lacking.

Methods

Nasal lavage fluid was collected from 11 patients with symptomatic allergic rhinitis and 11 healthy volunteers. 2-dimensional gel electrophoresis was used to separate proteins in the lavage fluids. Protein spots were picked from the gels and identified using mass spectrometry and database search. Selected proteins were confirmed with western blot.

Results

61 spots were identified, of which 21 were separate proteins. 6 of these proteins (psoriasin, galectin-3, alpha enolase, intersectin-2, Wnt-2B and hypothetical protein MGC33648) had not previously been described in nasal lavage fluids. The levels of psoriasin were markedly down-regulated in allergic individuals. Prolactin-inducible protein was also found to be down-regulated, whereas different fragments of albumin together with Ig gamma 2 chain c region, transthyretin and splice isoform 1 of Wnt-2B were up-regulated among the allergic patients.

Conclusion

The identification of proteins in nasal lavage fluid with 2-dimensional gelelectrophoresis in combination with mass spectrometry is a novel tool to profile protein expression in allergic rhinitis and it might prove useful in the hunt for new therapeutic targets or diagnostic markers for allergic diseases. Psoriasin is a potent chemotactic factor and its down-regulation during inflammation might be of importance for the outcome of the disease.
Liquid chromatography/mass spectrometry analysis of exhaled leukotriene B4 in asthmatic children
Authors: Montuschi Paolo , Martello Simona , Felli Marialinda , Mondino Chiara , Barnes Peter J , Chiarotti Marcello
Published: October 2005

Background

The role of leukotriene (LT) B4, a potent inflammatory mediator, in atopic asthmatic and atopic nonasthmatic children is largely unknown. The lack of a gold standard technique for measuring LTB4 in exhaled breath condensate (EBC) has hampered its quantitative assessment in this biological fluid. We sought to measure LTB4 in EBC in atopic asthmatic children and atopic nonasthmatic children. Exhaled nitric oxide (NO) was measured as an independent marker of airway inflammation.

Methods

Fifteen healthy children, 20 atopic nonasthmatic children, 25 steroid-naïve atopic asthmatic children, and 22 atopic asthmatic children receiving inhaled corticosteroids were studied. The study design was of cross-sectional type. Exhaled LTB4 concentrations were measured using liquid chromatography/mass spectrometry-mass spectrometry (LC/MS/MS) with a triple quadrupole mass spectrometer. Exhaled NO was measured by chemiluminescence with a single breath on-line method. LTB4 values were expressed as the total amount (in pg) of eicosanoid expired in the 15-minute breath test. Kruskal-Wallis test was used to compare groups.

Results

Compared with healthy children [87.5 (82.5–102.5) pg, median and interquartile range], exhaled LTB4 was increased in steroid-naïve atopic asthmatic [255.1 (175.0–314.7) pg, p < 0.001], but not in atopic nonasthmatic children [96.5 (87.3–102.5) pg, p = 0.59)]. Asthmatic children who were receiving inhaled corticosteroids had lower concentrations of exhaled LTB4 than steroid-naïve asthmatics [125.0 (25.0–245.0) pg vs 255.1 (175.0–314.7) pg, p < 0.01, respectively]. Exhaled NO was higher in atopic nonasthmatic children [16.2 (13.5–22.4) ppb, p < 0.05] and, to a greater extent, in atopic steroid-naïve asthmatic children [37.0 (31.7–57.6) ppb, p < 0.001] than in healthy children [8.3 (6.1–9.9) ppb]. Compared with steroid-naïve asthmatic children, exhaled NO levels were reduced in asthmatic children who were receiving inhaled corticosteroids [15.9 (11.5–31.7) ppb, p < 0.01].

Conclusion

In contrast to exhaled NO concentrations, exhaled LTB4 values are selectively elevated in steroid-naïve atopic asthmatic children, but not in atopic nonasthmatic children. Although placebo control studies are warranted, inhaled corticosteroids seem to reduce exhaled LTB4 in asthmatic children. LC/MS/MS analysis of exhaled LTB4 might provide a non-invasive, sensitive, and quantitative method for airway inflammation assessment in asthmatic children.
SpectralNET – an application for spectral graph analysis and visualization
Authors: Forman Joshua J , Clemons Paul A , Schreiber Stuart L , Haggarty Stephen J
Published: October 2005

Background

Graph theory provides a computational framework for modeling a variety of datasets including those emerging from genomics, proteomics, and chemical genetics. Networks of genes, proteins, small molecules, or other objects of study can be represented as graphs of nodes (vertices) and interactions (edges) that can carry different weights. SpectralNET is a flexible application for analyzing and visualizing these biological and chemical networks.

Results

Available both as a standalone .NET executable and as an ASP.NET web application, SpectralNET was designed specifically with the analysis of graph-theoretic metrics in mind, a computational task not easily accessible using currently available applications. Users can choose either to upload a network for analysis using a variety of input formats, or to have SpectralNET generate an idealized random network for comparison to a real-world dataset. Whichever graph-generation method is used, SpectralNET displays detailed information about each connected component of the graph, including graphs of degree distribution, clustering coefficient by degree, and average distance by degree. In addition, extensive information about the selected vertex is shown, including degree, clustering coefficient, various distance metrics, and the corresponding components of the adjacency, Laplacian, and normalized Laplacian eigenvectors. SpectralNET also displays several graph visualizations, including a linear dimensionality reduction for uploaded datasets (Principal Components Analysis) and a non-linear dimensionality reduction that provides an elegant view of global graph structure (Laplacian eigenvectors).

Conclusion

SpectralNET provides an easily accessible means of analyzing graph-theoretic metrics for data modeling and dimensionality reduction. SpectralNET is publicly available as both a .NET application and an ASP.NET web application from http://chembank.broad.harvard.edu/resources/. Source code is available upon request.
Lineage-specific variations of congruent evolution among DNA sequences from three genomes, and relaxed selective constraints on rbcL in Cryptomonas (Cryptophyceae)
Authors: Hoef-Emden Kerstin , Tran Hoang-Dung , Melkonian Michael
Published: October 2005

Background

Plastid-bearing cryptophytes like Cryptomonas contain four genomes in a cell, the nucleus, the nucleomorph, the plastid genome and the mitochondrial genome. Comparative phylogenetic analyses encompassing DNA sequences from three different genomes were performed on nineteen photosynthetic and four colorless Cryptomonas strains. Twenty-three rbc L genes and fourteen nuclear SSU rDNA sequences were newly sequenced to examine the impact of photosynthesis loss on codon usage in the rbc L genes, and to compare the rbc L gene phylogeny in terms of tree topology and evolutionary rates with phylogenies inferred from nuclear ribosomal DNA (concatenated SSU rDNA, ITS2 and partial LSU rDNA), and nucleomorph SSU rDNA.

Results

Largely congruent branching patterns and accelerated evolutionary rates were found in nucleomorph SSU rDNA and rbc L genes in a clade that consisted of photosynthetic and colorless species suggesting a coevolution of the two genomes. The extremely accelerated rates in the rbc L phylogeny correlated with a shift from selection to mutation drift in codon usage of two-fold degenerate NNY codons comprising the amino acids asparagine, aspartate, histidine, phenylalanine, and tyrosine. Cysteine was the sole exception. The shift in codon usage seemed to follow a gradient from early diverging photosynthetic to late diverging photosynthetic or heterotrophic taxa along the branches. In the early branching taxa, codon preferences were changed in one to two amino acids, whereas in the late diverging taxa, including the colorless strains, between four and five amino acids showed changes in codon usage.

Conclusion

Nucleomorph and plastid gene phylogenies indicate that loss of photosynthesis in the colorless Cryptomonas strains examined in this study possibly was the result of accelerated evolutionary rates that started already in photosynthetic ancestors. Shifts in codon usage are usually considered to be caused by changes in functional constraints and in gene expression levels. Thus, the increasing influence of mutation drift on codon usage along the clade may indicate gradually relaxed constraints and reduced expression levels on the rbc L gene, finally correlating with a loss of photosynthesis in the colorless Cryptomonas paramaecium strains.
Hydrophilic and lipophilic radiopharmaceuticals as tracers in pharmaceutical development: In vitro – In vivo studies
Authors: Terán Mariella , Savio Eduardo , Paolino Andrea , Frier Malcolm
Published: October 2005

Background

Scintigraphic studies have been performed to assess the release, both in vitro and in vivo, of radiotracers from tablet formulations. Four different tracers with differing physicochemical characteristics have been evaluated to assess their suitability as models for drug delivery.

Methods

In-vitro disintegration and dissolution studies have been performed at pH 1, 4 and 7. In-vivo studies have been performed by scintigraphic imaging in healthy volunteers. Two hydrophilic tracers, (99mTc-DTPA) and (99mTc-MDP), and two lipophilic tracers, (99mTc-ECD) and (99mTc-MIBI), were used as drug models.

Results

Dissolution and disintegration profiles, differed depending on the drug model chosen. In vitro dissolution velocity constants indicated a probable retention of the radiotracer in the formulation. In vivo disintegration velocity constants showed important variability for each radiopharmaceutical. Pearson statistical test showed no correlation between in vitro drug release, and in vivo behaviour, for 99mTc-DTPA, 99mTc-ECD and 99mTc-MIBI. High correlation coefficients were found for 99mTc-MDP not only for in vitro dissolution and disintegration studies but also for in vivo scintigraphic studies.

Conclusion

Scintigraphic studies have made a significant contribution to the development of drug delivery systems. It is essential, however, to choose the appropriate radiotracers as models of drug behaviour. This study has demonstrated significant differences in release patterns, depending on the model chosen. It is likely that each formulation would require the development of a specific model, rather than being able to use a generic drug model on the basis of its physicochemical characteristics.
Neuropsychological effects of chronic low-dose exposure to polychlorinated biphenyls (PCBs): A cross-sectional study
Authors: Peper Martin , Klett Martin , Morgenstern Rudolf
Published: October 2005

Background

Exposure to indoor air of private or public buildings contaminated with polychlorinated biphenyls (PCBs) has raised health concerns in long-term users. This exploratory neuropsychological group study investigated the potential adverse effects of chronic low-dose exposure to specific air-borne low chlorinated PCBs on well-being and behavioral measures in adult humans.

Methods

Thirty employees exposed to indoor air contaminated with PCBs from elastic sealants in a school building were compared to 30 non-exposed controls matched for education and age, controlling for gender (age range 37–61 years). PCB exposure was verified by external exposure data and biological monitoring (PCB 28, 101, 138, 153, 180). Subjective complaints, learning and memory, executive function, and visual-spatial function was assessed by standardized neuropsychological testing. Since exposure status depended on the use of contaminated rooms, an objectively exposed subgroup (N = 16; PCB 28 = 0.20 μg/l; weighted exposure duration 17.9 ± 7 years) was identified and compared with 16 paired controls.

Results

Blood analyses indicated a moderate exposure effect size (d) relative to expected background exposure for total PCB (4.45 ± 2.44 μg/l; d = 0.4). A significant exposure effect was found for the low chlorinated PCBs 28 (0.28 ± 0.25 μg/l; d = 1.5) and 101 (0.07 ± 0.09 μg/l; d = 0.7). Although no neuropsychological effects exceeded the adjusted significance level, estimation statistics showed elevated effect sizes for several variables. The objectively exposed subgroup showed a trend towards increased subjective attentional and emotional complaints (tiredness and slowing of practical activities, emotional state) as well as attenuated attentional performance (response shifting and alertness in a cued reaction task).

Conclusion

Chronic inhalation of low chlorinated PCBs that involved elevated blood levels was associated with a subtle attenuation of emotional well-being and attentional function. Extended research is needed to replicate the potential long-term low PCB effects in a larger sample.
Cannabis and tobacco smoke are not equally carcinogenic
Authors: Melamede Robert
Published: October 2005

More people are using the cannabis plant as modern basic and clinical science reaffirms and extends its medicinal uses. Concomitantly, concern and opposition to smoked medicine has occurred, in part due to the known carcinogenic consequences of smoking tobacco. Are these reactions justified? While chemically very similar, there are fundamental differences in the pharmacological properties between cannabis and tobacco smoke. Cannabis smoke contains cannabinoids whereas tobacco smoke contains nicotine. Available scientific data, that examines the carcinogenic properties of inhaling smoke and its biological consequences, suggests reasons why tobacco smoke, but not cannabis smoke, may result in lung cancer.
Post-ERCP pancreatogastric fistula associated with an intraductal papillary-mucinous neoplasm of the pancreas – a case report and literature review
Authors: Koizumi Masaru , Sata Naohiro , Yoshizawa Koji , Tsukahara Munetoshi , Kurihara Katsumi , Yasuda Yoshikazu , Nagai Hideo
Published: October 2005

Background

Fistula formation has been reported in intraductal papillary-mucinous neoplasms (IPMNs) with or without invasion of the adjacent organs. The presence or absence of invasion is mostly determined by postoperative histological examination rather than by preoperative work-up.

Case presentation

A 72 year-old Japanese woman showed remarkable dilatation of the main pancreatic duct (MPD) in the distal region of the pancreas. Subsequent ERCP also showed MPD dilatation, after which the patient suffered moderate pancreatitis. A subsequent gastroscopy revealed a small ulceration that had not been observed in a gastroscopy performed 3 months prior. Mucinous discharge from the ulceration suggested it might be the orifice of a fistula connected to the MPD. En bloc resection including the distal region of the pancreas, spleen, stomach and part of the transverse colon was performed under the pre- and intraoperative diagnosis of an invasive malignant IPMN. However, histopathology revealed the lesion to be of "borderline malignancy" without apparent invasion of the stomach. Light microscopy showed inflammatory cellular infiltrates (mainly neutrophils) around the pancreatogastric fistula, but there was no evidence of neoplastic epithelia lining the fistulous tract.

Conclusion

This case highlights that a pancreatogastric fistula can develop after acute inflammation of the pancreas in the absence of cancer invasion. Further information regarding IPMN-associated fistulae is necessary to clarify the pathogenesis, diagnosis, appropriate surgical intervention and prognosis for this disorder.
Feto-maternal biology and ethics of human society
Authors: Paulesu Luana , Ietta Francesca , Petraglia Felice
Published: October 2005

The growing interest in human reproduction and the identity of the embryo have prompted us to bring some considerations to the attention of scientists. In particular, we focus on the interactive relationship between the embryo and the mother starting from the earliest stages of development. Principles governing the acceptance and growth of the embryo in the uterus may represent a model for mutual tolerance and peaceful co-existence in human society.
Xenopus frizzled-4S, a splicing variant of Xfz4 is a context-dependent activator and inhibitor of Wnt/β-catenin signaling
Authors: Swain Rajeeb Kumar , Katoh Masaru , Medina Araceli , Steinbeisser Herbert
Published: October 2005

Background

S ecreted F rizzled r elated p roteins (SFRPs) are extracellular regulators of Wnt signaling. These proteins contain an N-terminal cysteine rich domain (CRD) highly similar to the CRDs of the Frizzled family of seven-transmembrane proteins that act as Wnt receptors. SFRPs can bind to Wnts and prevent their interaction with the Frizzled receptor. Recently it has been reported that a splice variant of human Frizzled-4 (FZD4S) lacking the transmembrane and the cytoplasmic domains of Frizzled-4 can activate rather than inhibit Wnt-8 activity in Xenopus embryos. This indicates that secreted CRD containing proteins such as Frizzled ecto-domains and SFRPs may not always act as Wnt inhibitors. It is not known how FZD4S can activate Wnt/β-catenin signaling and what biological role this molecule plays in vivo.

Results

Here we report that the Xenopus frizzled-4 is alternatively spliced to give rise to a putative secreted protein that lacks the seven-transmembrane and the cytoplasmic domains. We performed functional experiments in Xenopus embryos to investigate how this novel splicing variant, Xfz4S, can modulate the Wnt/β-catenin pathway. We show that Xfz4S as well as the extracellular domain of Xfz8 (ECD8) can act as both activators and inhibitors of Wnt/β-catenin signaling dependent on the Wnt ligand presented. The positive regulation of Wnt/β-catenin signaling by the extracellular domains of Frizzled receptors is mediated by the members of low density lipoprotein receptor-related protein (LRP-5/6) that act as Wnt coreceptors.

Conclusion

This work provides evidence that the secreted extracellular domains of Frizzled receptors may act as both inhibitors and activators of Wnt signaling dependent on the Wnt ligand presented.
Early correlation of microglial activation with enhanced tumor necrosis factor-alpha and monocyte chemoattractant protein-1 expression specifically within the entorhinal cortex of triple transgenic Alzheimer's disease mice
Authors: Janelsins Michelle C , Mastrangelo Michael A , Oddo Salvatore , LaFerla Frank M , Federoff Howard J , Bowers William J
Published: October 2005

Background

Alzheimer's disease is a complex neurodegenerative disorder characterized pathologically by a temporal and spatial progression of beta-amyloid (Aβ) deposition, neurofibrillary tangle formation, and synaptic degeneration. Inflammatory processes have been implicated in initiating and/or propagating AD-associated pathology within the brain, as inflammatory cytokine expression and other markers of inflammation are pronounced in individuals with AD pathology. The current study examines whether inflammatory processes are evident early in the disease process in the 3xTg-AD mouse model and if regional differences in inflammatory profiles exist.

Methods

Coronal brain sections were used to identify Aβ in 2, 3, and 6-month 3xTg-AD and non-transgenic control mice. Quantitative real-time RT-PCR was performed on microdissected entorhinal cortex and hippocampus tissue of 2, 3, and 6-month 3xTg-AD and non-transgenic mice. Microglial/macrophage cell numbers were quantified using unbiased stereology in 3xTg-AD and non-transgenic entorhinal cortex and hippocampus containing sections.

Results

We observed human Aβ deposition at 3 months in 3xTg-AD mice which is enhanced by 6 months of age. Interestingly, we observed a 14.8-fold up-regulation of TNF-α and 10.8-fold up-regulation of MCP-1 in the entorhinal cortex of 3xTg-AD mice but no change was detected over time in the hippocampus or in either region of non-transgenic mice. Additionally, this increase correlated with a specific increase in F4/80-positive microglia and macrophages in 3xTg-AD entorhinal cortex.

Conclusion

Our data provide evidence for early induction of inflammatory processes in a model that develops amyloid and neurofibrillary tangle pathology. Additionally, our results link inflammatory processes within the entorhinal cortex, which represents one of the earliest AD-affected brain regions.
Contribution of the C-terminal tri-lysine regions of human immunodeficiency virus type 1 integrase for efficient reverse transcription and viral DNA nuclear import
Authors: Ao Zhujun , Fowke Keith R , Cohen Éric A , Yao Xiaojian
Published: October 2005

Background

In addition to mediating the integration process, HIV-1 integrase (IN) has also been implicated in different steps during viral life cycle including reverse transcription and viral DNA nuclear import. Although the karyophilic property of HIV-1 IN has been well demonstrated using a variety of experimental approaches, the definition of domain(s) and/or motif(s) within the protein that mediate viral DNA nuclear import and its mechanism are still disputed and controversial. In this study, we performed mutagenic analyses to investigate the contribution of different regions in the C-terminal domain of HIV-1 IN to protein nuclear localization as well as their effects on virus infection.

Results

Our analysis showed that replacing lysine residues in two highly conserved tri-lysine regions, which are located within previously described Region C (235WKGPAKLLWKGEGAVV) and sequence Q (211KELQKQITK) in the C-terminal domain of HIV-1 IN, impaired protein nuclear accumulation, while mutations for RK263,4 had no significant effect. Analysis of their effects on viral infection in a VSV-G pseudotyped RT/IN trans-complemented HIV-1 single cycle replication system revealed that all three C-terminal mutant viruses (KK215,9AA, KK240,4AE and RK263,4AA) exhibited more severe defect of induction of β-Gal positive cells and luciferase activity than an IN class 1 mutant D64E in HeLa-CD4-CCR5-β-Gal cells, and in dividing as well as non-dividing C8166 T cells, suggesting that some viral defects are occurring prior to viral integration. Furthermore, by analyzing viral DNA synthesis and the nucleus-associated viral DNA level, the results clearly showed that, although all three C-terminal mutants inhibited viral reverse transcription to different extents, the KK240,4AE mutant exhibited most profound effect on this step, whereas KK215,9AA significantly impaired viral DNA nuclear import. In addition, our analysis could not detect viral DNA integration in each C-terminal mutant infection, even though they displayed various low levels of nucleus-associated viral DNA, suggesting that these C-terminal mutants also impaired viral DNA integration ability.

Conclusion

All of these results indicate that, in addition to being involved in HIV-1 reverse transcription and integration, the C-terminal tri-lysine regions of IN also contribute to efficient viral DNA nuclear import during the early stage of HIV-1 replication.
DBR1 siRNA inhibition of HIV-1 replication
Authors: Ye Ying , De Leon Jessica , Yokoyama Noriko , Naidu Yathi , Camerini David
Published: October 2005

Background

HIV-1 and all retroviruses are related to retroelements of simpler organisms such as the yeast Ty elements. Recent work has suggested that the yeast retroelement Ty1 replicates via an unexpected RNA lariat intermediate in cDNA synthesis. The putative genomic RNA lariat intermediate is formed by a 2'-5' phosphodiester bond, like that found in pre-mRNA intron lariats and it facilitates the minus-strand template switch during cDNA synthesis. We hypothesized that HIV-1 might also form a genomic RNA lariat and therefore that siRNA-mediated inhibition of expression of the human RNA lariat de-branching enzyme (DBR1) expression would specifically inhibit HIV-1 replication.

Results

We designed three short interfering RNA (siRNA) molecules targeting DBR1, which were capable of reducing DBR1 mRNA expression by 80% and did not significantly affect cell viability. We assessed HIV-1 replication in the presence of DBR1 siRNA and found that DBR1 knockdown led to decreases in viral cDNA and protein production. These effects could be reversed by cotransfection of a DBR1 cDNA indicating that the inhibition of HIV-1 replication was a specific effect of DBR1 underexpression.

Conclusion

These data suggest that DBR1 function may be needed to debranch a putative HIV-1 genomic RNA lariat prior to completion of reverse transcription.
Between adaptive and innate immunity: TLR4-mediated perforin production by CD28nullT-helper cells in ankylosing spondylitis
Authors: Raffeiner Bernd , Dejaco Christian , Duftner Christina , Kullich Werner , Goldberger Christian , Vega Sandra C , Keller Michael , Grubeck-Loebenstein Beatrix , Schirmer Michael
Published: October 2005

CD3+CD4+CD28null and CD3+CD8+CD28null T cells are enriched in patients with immune-mediated diseases compared with healthy controls. This study shows that CD4+CD28null T cells express Toll-like receptors recognizing bacterial lipopolysaccharides in ankylosing spondylitis, psoriatic arthritis and rheumatoid arthritis. In ankylosing spondylitis, TLR4 (23.1 ± 21.9%) and, to a smaller extent, TLR2 (4.1 ± 5.8%) were expressed on CD4+CD28null T cells, whereas expression was negligible on CD4+CD28+ and CD8+ T cells. CD4+CD28null T cells produced perforin upon stimulation with lipopolysaccharide, and this effect was enhanced by autologous serum or recombinant soluble CD14. Perforin production could be prevented with blocking antibodies directed against CD14 or TLR4. Incubation of peripheral blood mononuclear cells with tumour necrosis factor alpha led to an upregulation of TLR4 and TLR2 on CD4+CD28null T cells in vitro, and treatment of patients with antibodies specifically directed against tumour necrosis factor alpha resulted in decreased expression of TLR4 and TLR2 on CD4+CD28null T cells in vivo. We describe here a new pathway for direct activation of cytotoxic CD4+ T cells by components of infectious pathogens. This finding supports the hypothesis that CD4+CD28null T cells represent an immunological link between the innate immune system and the adaptive immune system.
Identification of citrullinated α-enolase as a candidate autoantigen in rheumatoid arthritis
Authors: Kinloch Andrew , Tatzer Verena , Wait Robin , Peston David , Lundberg Karin , Donatien Phillipe , Moyes David , Taylor Peter C , Venables Patrick J
Published: October 2005

Antibodies against citrullinated proteins are highly specific for rheumatoid arthritis (RA), but little is understood about their citrullinated target antigens. We have detected a candidate citrullinated protein by immunoblotting lysates of monocytic and granulocytic HL-60 cells treated with peptidylarginine deiminase. In an initial screen of serum samples from four patients with RA and one control, a protein of molecular mass 47 kDa from monocytic HL-60s reacted with sera from the patients, but not with the serum from the control. Only the citrullinated form of the protein was recognised. The antigen was identified by tandem mass spectrometry as α-enolase, and the positions of nine citrulline residues in the sequence were determined. Serum samples from 52 patients with RA and 40 healthy controls were tested for presence of antibodies against citrullinated and non-citrullinated α-enolase by immunoblotting of the purified antigens. Twenty-four sera from patients with RA (46%) reacted with citrullinated α-enolase, of which seven (13%) also recognised the non-citrullinated protein. Six samples from the controls (15%) reacted with both forms. α-Enolase was detected in the RA joint, where it co-localised with citrullinated proteins. The presence of antibody together with expression of antigen within the joint implicates citrullinated α-enolase as a candidate autoantigen that could drive the chronic inflammatory response in RA.
Chromatin and siRNA pathways cooperate to maintain DNA methylation of small transposable elements in Arabidopsis
Authors: Tran Robert K , Zilberman Daniel , de Bustos Cecilia , Ditt Renata F , Henikoff Jorja G , Lindroth Anders M , Delrow Jeffrey , Boyle Tom , Kwong Samson , Bryson Terri D , Jacobsen Steven E , Henikoff Steven
Published: October 2005

Background

DNA methylation occurs at preferred sites in eukaryotes. In Arabidopsis, DNA cytosine methylation is maintained by three subfamilies of methyltransferases with distinct substrate specificities and different modes of action. Targeting of cytosine methylation at selected loci has been found to sometimes involve histone H3 methylation and small interfering (si)RNAs. However, the relationship between different cytosine methylation pathways and their preferred targets is not known.

Results

We used a microarray-based profiling method to explore the involvement of Arabidopsis CMT3 and DRM DNA methyltransferases, a histone H3 lysine-9 methyltransferase (KYP) and an Argonaute-related siRNA silencing component (AGO4) in methylating target loci. We found that KYP targets are also CMT3 targets, suggesting that histone methylation maintains CNG methylation genome-wide. CMT3 and KYP targets show similar proximal distributions that correspond to the overall distribution of transposable elements of all types, whereas DRM targets are distributed more distally along the chromosome. We find an inverse relationship between element size and loss of methylation in ago4 and drm mutants.

Conclusion

We conclude that the targets of both DNA methylation and histone H3K9 methylation pathways are transposable elements genome-wide, irrespective of element type and position. Our findings also suggest that RNA-directed DNA methylation is required to silence isolated elements that may be too small to be maintained in a silent state by a chromatin-based mechanism alone. Thus, parallel pathways would be needed to maintain silencing of transposable elements.
Design of the Dialysis Access Consortium (DAC) Aggrenox prevention of access stenosis trial
Authors: Dixon Bradley S , Beck Gerald J , Dember Laura M , Depner Thomas A , Gassman Jennifer J , Greene Tom , Himmelfar Jonathan , Hunsicker Lawrence G , Kaufman James S , Lawson Jeffrey H , Meyers Catherine M , Middleton John P , Radeva Milena , Schwab Steve J , Whiting James F , Feldman Harold I
Published: October 2005

Background Surgically created arteriovenous (AV) grafts are the most common type of hemodialysis vascular access in the United States, but fail frequently due to the development of venous stenosis. The Dialysis Access Consortium (DAC) Aggrenox Prevention of Access Stenosis Trial tests the hypothesis that Aggrenox (containing dipyridamole and aspirin) can prevent stenosis and prolong survival of arteriovenous grafts.

Methods This is a multicenter, randomized, double-blind, placebo-controlled trial that will enroll 1056 subjects over four years with one-half year follow-up. Subjects undergoing placement of a new AV graft for hemodialysis are randomized to treatment with Aggrenox or placebo immediately following access surgery. The primary outcome is primary unassisted patency defined as the time from access placement until thrombosis or an access procedure carried out to maintain or restore patency. The major secondary outcome is cumulative access patency. Monthly access flow monitoring is incorporated in the study design to enhance detection of a hemodynamically significant access stenosis before it leads to thrombosis.

Results This paper describes the key issues in trial design, broadly including: 1) ethical issues surrounding the study of a clinical procedure that, although common, is no longer the clinical intervention of choice; 2) acceptable risk (bleeding) from the primary intervention; 3) inclusion of subjects already receiving a portion of the study intervention; 4) inclusion of subjects with incident rather than prevalent qualifying clinical conditions; 5) timing of the study intervention to balance safety and efficacy concerns; and 6) the selection of primary and secondary study endpoints.

Conclusions This is the first, large, multicenter trial evaluating a pharmacologic approach to prevent AV graft stenosis and failure, an important and costly problem in this patient population. Numerous design issues were addressed in implementing the trial and these will form a roadmap for future trials in this area.
Decision rule based multiplicity adjustment strategy
Authors: Chen Xun , Capizzi Tom , Binkowitz Bruce , Quan Hui , Wei Lynn , Luo Xiaohui
Published: October 2005

To minimize potential controversies in determining the need for multiplicity adjustment for multiple hypotheses, we propose a decision rule based multiplicity adjustment strategy in this paper. Resorting to a predefined decision rule of a clinical trial, one may link the different hypotheses by their logical relationships and divide them into different families. A proper multiplicity adjustment procedure can then be developed by maintaining strong control of Type I error rate within each family. The paper applies the proposed multiplicity adjustment strategy to a published raloxifene clinical trial.
Design of the Dialysis Access Consortium (DAC) clopidogrel prevention of early AV fistula thrombosis trial
Authors: Dember Laura M , Kaufman James S , Beck Gerald J , Dixon Bradley S , Gassman Jennifer J , Greene Tom , Himmelfarb Jonathan , Hunsicker Lawrence G , Kusek John W , Lawson Jeffrey H , Middleton John P , Radeva Milena , Schwab Steve J , Whiting James F , Feldman Harold I
Published: October 2005

Background The Dialysis Access Consortium (DAC) was developed to investigate interventions to improve hemodialysis vascular access outcomes. The autogenous arteriovenous fistula created by direct connection of native artery to vein is the recommended vascular access for hemodialysis. However, it fails frequently due to clotting after surgery.

Purpose The DAC Early AV Fistula Thrombosis Trial tests the hypothesis that clopidogrel can prevent early fistula failure and increase the number of fistulas that ultimately become usable for hemodialysis access. This is one of two initial and concurrent trials being performed by the DAC. The companion trial investigates pharmacologic approaches to prevent venous stenosis leading to AV graft failure.

Methods This is a multicenter, randomized, double-blind, placebo-controlled trial that will enroll 1284 patients over four years. Patients undergoing creation of a new native arteriovenous (AV) fistula are randomized to treatment with clopidogrel or placebo for six weeks following fistula creation surgery. The primary outcome is fistula patency at six weeks. The major secondary outcome is fistula suitability for dialysis.

Results This paper examines key aspects of this study that have broad relevance to trial design including: 1) the selection of an intermediate event as the primary outcome, 2) timing of the intervention to balance efficacy and safety concerns, 3) ethical considerations arising from required modifications of concomitant drug therapy, and 4) choosing an efficacy or effectiveness evaluation of the intervention.

Conclusions This is the first, large, multicenter trial evaluating a pharmacologic approach to prevent early AV fistula failure and promote more usable fistulas for hemodialysis. The methodologic challenges identified and addressed during the development of this trial should help to inform the design of future vascular access trials, and are relevant to clinical trials addressing a wide range of questions.
2005 Teaching Award Winners
Authors: Hammer Elizabeth Yost
Published: October 2005

The Society for the Teaching of Psychology (Division Two) celebrated the 26th year of its annual Teaching Awards Program at the August convention of the American Psychological Association in Washington, D.C. The 2005 winners received a plaque and a check for 750. Recognition for outstanding teaching was given in each of the following categories: (a) Robert S. Daniel Award (4-year college or university professor), (b) 2-year College Award, (c) Moffett Memorial Award (high school teacher), and (d) McKeachie Graduate Student Teaching Excellence Award.
Learning and Motivational Benefits of Acronym Use in Introductory Psychology
Authors: Stalder Daniel R.
Published: October 2005

Study 1 assessed students' use and perceptions of acronyms at 3 different exam times in 2 sections of Introduction to Psychology. Acronym use consistently predicted higher performance on acronym-related exam items, and I partially discounted 2 possible confounds. Students rated acronyms as helpful in multiple ways, including increasing motivation to begin studying. Students reported low prior use of acronyms, created their own acronyms during the semester, and conveyed intentions to continue mnemonic use on their own in later classes. Study 2 assessed psychology instructors' use and views of acronyms. I also provide a list of acronyms for introductory psychology and discuss general considerations in the construction and classroom use of acronyms.
Authorized Crib Cards Do Not Improve Exam Performance
Authors: Dickson K. Laurie , Miller Michelle D.
Published: October 2005

We experimentally investigated the effect of authorized crib cards on undergraduates' multiple-choice exam performance for lower order and higher order questions and on anxiety levels in an upper division child and adolescent development course. Students ( N = 54) in 2 sections could use crib cards during 2 of the 4 exams. Despite student expectations that crib cards would greatly improve performance and reduce anxiety, their use did not improve performance for either the higher order or lower order exam questions, nor did they reduce student anxiety. The failure of authorized crib cards to improve exam performance even for factual material suggests that instructors ought to weigh seriously the decision to allow such cards on exams.
Teaching the Principles of Test Validation in Introductory Psychology
Authors: Wesp Richard , Eshun Sussie
Published: October 2005

We describe a simple classroom activity that demonstrated the process of assessing predictive validity. We assessed changes in student understanding of the process, confidence in psychological testing, and enjoyment in participating in the exercise. Students who completed the activity performed better on a test question about validity and reported more confidence in testing. Students reported they enjoyed the exercise and that the activity provided them with a better understanding of the test development process.
Electronic Discussion Sections: A Useful Tool in Teaching Large University Classes
Authors: Bryant Brenda K.
Published: October 2005

Electronic discussion sections can create a learning environment that will elicit quality student discussions in classes with large enrollment (i.e., 100 to 150 students). Redressing problems encountered during the first year using electronic discussions, I made changes such as establishing grading criteria for evaluating each student contribution to discussion, rules of etiquette, and discussion group size. The quality of intellectual discussions was better in Year 2 than in Year 1. There was no relation between initial computer phobia of students and their academic performance in classes requiring computer usage for electronic discussions. Data also revealed comparable quality of electronic discussions in a lower division, general education class as in an upper division class.
Situated Action: A Symbolic Interpretation
Authors: Vera Alonso H. , Simon Herbert A.
Published: October 2005

The congeries of theoretical views collectively referred to as “situated action” (SA) claim that humans and their interactions with the world cannot be understood using symbol‐system models and methodology, but only by observing them within real‐world contexts or building nonsymbolic models of them. SA claims also that rapid, real‐time interaction with a dynamically changing environment is not amenable to symbolic interpretation of the sort espoused by the cognitive science of recent decades. Planning and representation, central to symbolic theories, are claimed to be irrelevant in everyday human activity.

We will contest these claims, as well as their proponents' characterizations of the symbol‐system viewpoint. We will show that a number of existing symbolic systems perform well in temporally demanding tasks embedded in complex environments, whereas the systems usually regarded as exemplifying SA are thoroughly symbolic (and representational), and, to the extent that they are limited in these respects, have doubtful prospects for extension to complex tasks. As our title suggests, we propose that the goals set forth by the proponents of SA can be attained only within the framework of symbolic systems. The main body of empirical evidence supporting our view resides in the numerous symbol systems constructed in the past 35 years that have successfully simulated broad areas of human cognition.
Microsurgical Anatomy and Quantitative Analysis of the Transtemporal-Transchoroidal Fissure Approach to the Ambient Cistern
Authors: Siwanuwatn Rungsak , Deshmukh Pushpa , Zabramski Joseph M. , Preul Mark C. , Spetzler Robert F.
Published: October 2005

OBJECTIVE:

Surgical approaches to ambient cistern lesions are complex. We investigated the microanatomy of the transtemporal-transchoroidal fissure approach to the ambient cistern with emphasis on exposure of the posterior cerebral artery.

METHODS:

Dissections were performed bilaterally in five silicone-injected cadaveric heads. Critical anatomic distances, specifically with reference to the P2 segment of posterior cerebral artery in relation to the inferior choroidal point and P2–P3 junction, were measured with digital calipers. Other landmarks (temporal lobe tip, points from the temporal base to the choroidal fissure) were included for quantitative analysis.

RESULTS:

The transtemporal-transchoroidal fissure approach provided adequate exposure of the ambient cistern, minimized temporal lobe retraction, and allowed assessment of regional microanatomy. The mean distance from the temporal base to the choroidal fissure measured 18.09 mm (range, 16.9–21.9 mm). The distances from the choroidal fissure to P2 varied at the coronal plane of the inferior choroidal point (mean, 6.96 mm; range, 3.6–12.0 mm) and the P2–P3 junction (mean, 6.02 mm; range, 4.3–6.9 mm), respectively.

CONCLUSION:

The transtemporal-transchoroidal fissure approach provides a corridor to the ambient cistern and P2–P3 junction while minimizing temporal lobe retraction and avoiding interruption of temporal lobe venous drainage. Because of widely variable vascular anatomy, access to posterior cerebral artery lesions using this approach requires preoperative imaging to identify the specific location of the P2–P3 junction.
Olfactory Groove Meningiomas from Neurosurgical and Ear, Nose, and Throat Perspectives: Approaches, Techniques, and Outcomes
Authors: Spektor Sergey , Valarezo Javier , Fliss Dan M. , Gil Ziv , Cohen Jose , Goldman Jose , Umansky Felix
Published: October 2005

OBJECTIVE:

To review the surgical approaches, techniques, outcomes, and recurrence rates in a series of 80 olfactory groove meningioma (OGM) patients operated on between 1990 and 2003.

METHODS:

Eighty patients underwent 81 OGM surgeries. Tumor diameter varied from 2 to 9 cm (average, 4.6 cm). In 35 surgeries (43.2%), the tumor was removed through bifrontal craniotomy; nine operations (11.1%) were performed through a unilateral subfrontal approach; 18 surgeries (22.2%) were performed through a pterional approach; seven surgeries (8.6%) were carried out using a fronto-orbital craniotomy; and 12 procedures (14.8%) were accomplished via a subcranial approach. Nine patients (11.3%) had undergone surgery previously and had recurrent tumor.

RESULTS:

Total removal was obtained in 72 patients (90.0%); subtotal removal was achieved in 8 patients (10.0%). Two patients, one with total and one with subtotal removal, had atypical (World Health Organization Grade II) meningiomas, whereas 78 patients had World Health Organization Grade I tumors. There was no operative mortality and no new permanent focal neurological deficit besides anosmia. Twenty-five patients (31.3%) experienced surgery-related complications. There were no recurrences in 75 patients (93.8%) 6 to 164 months (mean, 70.8 mo) after surgery. Three patients (3.8%) were lost to follow-up. In two patients (2.5%) with subtotal removal, the residual evidenced growth on computed tomography and/or magnetic resonance imaging 1 year after surgery. One of them had an atypical meningioma. The second, a multiple meningiomata patient, was operated on twice in this series.

CONCLUSION:

A variety of surgical approaches are used for OGM resection. An approach tailored to the tumor's size, location, and extension, combined with modern microsurgical cranial base techniques, allows full OGM removal with minimal permanent morbidity, excellent neurological outcome, and very low recurrence rates.
Artificial Pedicle Screw Reconstruction of the Cervical Spine after Lateral Paramedian Transpedicular Approach for Lesions of the Ventral Cervical Spinal Canal
Authors: Acosta Frank L. , Ames Christopher P.
Published: October 2005

OBJECTIVE:

We describe in detail the anatomic and surgical principles of a lateral cervical paramedian transpedicular approach, a novel technique that provides access to the ventral cervical spinal canal. We also describe single-stage posterior column reconstruction of the cervical spine in which traditional cervical lateral mass screws are used simultaneously to reconstruct the cervical pedicle and to allow for three-column stabilization in a continuous posterior screw-rod construct after this approach.

METHODS:

This technique is a modification of traditional thoracic posterolateral extracavitary approaches and has been used by our group for the resection of intradural and extradural spinal lesions, as we illustrate.

RESULTS:

This approach is particularly useful in cases where significant pathological characteristics of the trachea or esophagus preclude an anterior approach to the cervical spine and in cases in which multiple levels are involved.

CONCLUSION:

Cervical spinal stability is enhanced, because all cervical levels are incorporated into the final screw-rod construct.