bluuebunny/crossref_metadata_2025 huggingface dataset:
Implicit, Intuitive, and Explicit Knowledge of Abstract Regularities in a Sound Sequence: An Event-related Brain Potential Study
Authors: van Zuijen Titia L. , Simoens Veerle L. , Paavilainen Petri , Näätänen Risto , Tervaniemi Mari
Published: July 2006

Implicit knowledge has been proposed to be the substrate of intuition because intuitive judgments resemble implicit processes. We investigated whether the automatically elicited mismatch negativity (MMN) component of the auditory event-related potentials (ERPs) can reflect implicit knowledge and whether this knowledge can be utilized for intuitive sound discrimination. We also determined the sensitivity of the attention-and task-dependent P3 component to intuitive versus explicit knowledge. We recorded the ERPs elicited in an “abstract” oddball paradigm. Tone pairs roving over different frequencies but with a constant ascending inter-pair interval, were presented as frequent standard events. The standards were occasionally replaced by deviating, descending tone pairs. The ERPs were recorded under both ignore and attend conditions. Subjects were interviewed and classified on the basis of whether or not they could datect the deviants. The deviants elicited an MMN even in subjects who subsequent to the MMN recording did not express awareness of the deviants. This suggests that these subjects possessed implicit knowledge of the sound-sequence structure. Some of these subjects learned, in an associative training session, to detect the deviants intuitively, that is, they could detect the deviants but did not give a correct description of how the deviants differed from the standards. Intuitive deviant detection was not accompanied by P3 elicitation whereas subjects who developed explicit knowledge of the sound sequence during the training did show a P3 to the detected deviants.
Modulation of Face-sensitive Event-related Potentials by Canonical and Distorted Human Faces: The Role of Vertical Symmetry and Up-Down Featural Arrangement
Authors: Cassia Viola Macchi , Kuefner Dana , Westerlund Alissa , Nelson Charles A.
Published: July 2006

This study examined the sensitivity of early face-sensitive event-related potential (ERP) components to the disruption of two structural properties embedded in faces, namely, “updown featural arrangement” and “vertical symmetry.” Behavioral measures and ERPs were recorded as adults made an orientation judgment for canonical faces and distorted faces that had been manipulated for either or both of the mentioned properties. The P1, the N170, and the vertex positive potential (VPP) exhibited a similar gradient in sensitivity to the two investigated properties, in that they all showed a linear increase in amplitude or latency as the properties were selectively disrupted in the order of (1) up-down featural arrangement, (2) vertical symmetry, and (3) both up-down featural arrangement and vertical symmetry. Exceptions to this finding were seen for the amplitudes of the N170 and VPP, which were largest for the stimulus in which solely vertical symmetry was disrupted. Interestingly, the enhanced amplitudes of the N170 and VPP are consistent with a drop in behavioral performance on the orientation judgment for this stimulus.
The Role of Harmonic Expectancy Violations in Musical Emotions: Evidence from Subjective, Physiological, and Neural Responses
Authors: Steinbeis Nikolaus , Koelsch Stefan , Sloboda John A.
Published: July 2006

The purpose of the present study was to investigate the effect of harmonic expectancy violations on emotions. Subjective response measures for tension and emotionality, as well as electrodermal activity (EDA) and heart rate (HR), were recorded from 24 subjects (12 musicians and 12 nonmusicians) to observe the effect of expectancy violations on subjective and physiological measures of emotions. In addition, an electro-encephalogram was recorded to observe the neural correlates for detecting these violations. Stimuli consisted of three matched versions of six Bach chorales, which differed only in terms of one chord (harmonically either expected, unexpected or very unexpected). Musicians' and nonmusicians' responses were also compared. Tension, overall subjective emotionality, and EDA increased with an increase in harmonic unexpectedness. Analysis of the event-related potentials revealed an early negativity (EN) for both the unexpected and the very unexpected harmonies, taken to reflect the detection of the unexpected event. The EN in response to very unexpected chords was significantly larger in amplitude than the EN in response to merely unexpected harmonic events. The ENs did not differ in amplitude between the two groups but peaked earlier for musicians than for nonmusicians. Both groups also showed a P3 component in response to the very unexpected harmonies, which was considerably larger for musicians and may reflect the processing of stylistic violations of Western classical music.
Choice and Ego-Depletion: The Moderating Role of Autonomy
Authors: Moller Arlen C. , Deci Edward L. , Ryan Richard M.
Published: July 2006

The self-regulatory strength model maintains that all acts of self-regulation, self-control, and choice result in a state of fatigue called ego-depletion. Self-determination theory differentiates between autonomous regulation and controlled regulation. Because making decisions represents one instance of self-regulation, the authors also differentiate between autonomous choice and controlled choice. Three experiments support the hypothesis that whereas conditions representing controlled choice would be egodepleting, conditions that represented autonomous choice would not. In Experiment 3, the authors found significant mediation by perceived self-determination of the relation between the choice condition (autonomous vs. controlled) and ego-depletion as measured by performance.
Self-Conscious Emotions and Self-Regulation in the Promotion of Condom Use
Authors: Hynie Michaela , MacDonald Tara K. , Marques Sandra
Published: July 2006

Two prospective studies examined the self-regulatory role of anticipated negative self-conscious emotions (ANSCE) in the theory of planned behavior. In Study 1, 147 undergraduates reported condom attitudes, perceived norms, self-efficacy, ANSCE (shame and guilt) should they not use condoms, and intentions to use condoms during the coming 6 weeks. At a 6-week follow-up, ANSCE predicted condom use intentions and behavior and partially mediated the effect of attitudes and norms on both. Study 2 experimentally tested the social nature of self-consciousness in ANSCE; 61 female undergraduates read a scenario priming the private-self or social-self or were assigned to a no-scenario control. They reported condom attitudes, perceived control, ANSCE, condom use intentions, and a 6-week follow-up. ANSCE again predicted condom use intentions. A test of moderated mediation indicated that ANSCE influenced condom intentions more in the social-self condition than in the control condition. Implications of these findings are discussed.
Sexual Orientation Identity and Romantic Relationship Quality in Same-Sex Couples
Authors: Mohr Jonathan J. , Fassinger Ruth E.
Published: July 2006

Research suggests that the well-being of members of stigmatized groups is related to the ways that individuals understand, evaluate, and respond to their devalued collective identity. The present study extends this line of inquiry by investigating collective identity in the context of romantic relationship functioning, focusing on same-sex couples as a type of stigmatized relationship. In this cross-sectional study, the authors examined four identity-related variables (internalized homonegativity, stigma sensitivity, identity confusion, and identity superiority) in a sample of 274 female and 187 male same-sex couples. Results provided evidence of identity similarity between partners, particularly for internalized homonegativity and identity superiority. Each of the identity variables was associated with relationship quality, and actor effects of identity on quality were more common than partner effects. Perceived identity similarity mediated some of the links found between identity and quality and was positively associated with relationship quality regardless of actor identity.
On the Causal Mechanisms of Stereotype Threat: Can Skills That Don't Rely Heavily on Working Memory Still Be Threatened?
Authors: Beilock Sian L. , Jellison William A. , Rydell Robert J. , McConnell Allen R. , Carr Thomas H.
Published: July 2006

Recent work suggests that stereotype threat (ST) harms performance by reducing available working memory capacity. Is this the only mechanism by which ST can occur? Three experiments examined ST's impact on expert golf putting, which is not harmed when working memory is reduced but is hurt when attention is allocated to proceduralized processes that normally run outside working memory. Experiment 1 showed that well learned golf putting is susceptible to ST. Experiments 2 and 3 demonstrated that giving expert golfers a secondary task eliminates ST-induced impairment. Distracting attention away from the stereotype-related behavior eliminates the harmful impact of negative stereotype activation. These results are consistent with explicit monitoring theories of choking under pressure, which suggest that performance degradation can occur when too much attention is allocated to processes that usually run more automatically. Thus, ST alters information processing in multiple ways, inducing performance decrements for different reasons in different tasks.
Exaggerating Current and Past Performance: Motivated Self-Enhancement Versus Reconstructive Memory
Authors: Gramzow Richard H. , Willard Greg
Published: July 2006

The authors propose distinct reasons why individuals exaggerate their current and past performance. Current performance is of motivational and self-evaluative significance, and exaggerations of current performance often stem from motivated self-enhancement concerns. Self-reports of past performance are influenced less by motivated self-enhancement, instead reflecting more subtle biases in reconstructive memory. For students currently in college, grade point averages (GPAs) reflect a currently important goal pursuit, whereas Scholastic Aptitude Test (SAT) scores reflect a goal that was important in the past. Study 1 demonstrated that dispositional self-enhancement predicted greater GPA (but not SAT) exaggeration, whereas advanced class standing predicted greater SAT (but not GPA) exaggeration. Study 2 demonstrated that a self-affirmation manipulation attenuated the association between dispositional self-enhancement and GPA exaggeration but not the association between class standing and SAT exaggeration. The distinction between motivated self-enhancement and reconstructive memory bias has important implications for the broader literature on self-evaluation.
Calypso to Collapso
Authors: Griggs Gerald
Published: July 2006

Between 1974 and 1991, the West Indies cricket team reigned supreme. Between these years, the West Indies set many records including the longest unbeaten run in test history (27 matches 1982 to 1984) and managed a period of 15 years without losing a test series. Since then, a rapid decline has occurred. The purpose of this study is to examine the reasons as to why the West Indies cricket team has appeared to decline and has done so at such a rapid rate. The study looks for reasons beyond the populist idea that Americanization is to blame and identifies underlying political and historical factors that originate back to the formation of the West Indies, reasons that have been masked during the period of the team's success.
Social Support Among Afro-Trinidadian Women Experiencing Intimate Partner Violence
Authors: Hadeed Linda F. , El-Bassel Nabila
Published: July 2006

This study examines the types of, availability of, use of, and satisfaction with informal and formal social supports among Afro-Trinidadian women who have experienced intimate partner violence. A total of 17 women participated in a 2-hour, face-to-face interview. The findings suggest that despite male dominance and control, women were able to maintain some contact with family and friends. Although some women felt they had family and friends to turn to, many were dissatisfied with the support. Women also expressed dissatisfaction with legal and social services.
Whither Fema? Hurricane Katrina and FEMA's Response to the Gulf Coast
Authors: Morris John C.
Published: July 2006

The devastation caused by Hurricane Katrina in August 2005 placed the Federal Emergency Management Agency (FEMA) directly in the public spotlight. The agency came under tremendous criticism for its response, and its director resigned shortly after the hurricane. This article identifies and develops four themes (organizational location, organizational leadership, organizational emphasis, and federalism) drawn from the general literature in public administration and emergency management to provide a framework with which to analyze FEMA's post-Katrina responses and to place criticisms of the agency into a broader context.
Live Action Role-Playing Games
Authors: Tychsen Anders , Hitchens Michael , Brolund Thea , Kavakli Manolya
Published: July 2006

Live action role-playing games share a range of characteristics with massively multi-player online games (MMOGs). Because these games have existed for more than 20 years, players of these games have a substantial amount of experience in handling issues pertinent to MMOGs. Survey and review of live action role-playing games, whose participant count can be in the thousands, reveal that features such as size, theme, game master-to-player ratio, and others interact to form complex systems that require several different groups of control tools to manage. The way that these games are managed offers a variety of venues for further research into how these management techniques can be applied to MMOGs.
Gender imbalance and risk factor interactions in heparin-induced thrombocytopenia
Authors: Warkentin Theodore E. , Sheppard Jo-Ann I. , Sigouin Christopher S. , Kohlmann Thomas , Eichler Petra , Greinacher Andreas
Published: July 2006

Heparin-induced thrombocytopenia (HIT) is caused by antibodies against a “self” protein—platelet factor 4—bound to heparin. We observed an overrepresentation of the female gender in 290 patients who developed HIT after cardiac or orthopedic surgery compared with the representation found in national databases (study 1). Therefore, we investigated gender imbalance in HIT by logistic regression analysis of a randomized controlled trial of unfractionated heparin (UFH) and low-molecular-weight heparin (LMWH) (study 2), and we analyzed individual patient data from 7 prospective studies comparing HIT frequency between UFH and LMWH, evaluating effects of gender, heparin (UFH vs LMWH), and patient type (surgical vs medical) (study 3). All 3 studies showed female overrepresentation, which for study 3 was a common odds ratio (OR) of 2.37 (95% confidence interval [95% CI], 1.37-4.09; P = .0015). Study 3 also showed an interaction between gender, heparin, and patient type. Although UFH was more likely than LMWH to cause HIT (P < .0001), this effect was predominantly seen in women compared with men (common OR, 9.22 vs 1.83; P = .020) and in surgical patients compared with medical patients (common OR, 13.93 vs 1.75; P = .005). We conclude that females are at greater risk for HIT and that using LMWH to prevent HIT may have greatest absolute benefit in females undergoing surgical thromboprophylaxis.
SDF-1α regulation in breast cancer cells contacting bone marrow stroma is critical for normal hematopoiesis
Authors: Moharita Anabella L. , Taborga Marcelo , Corcoran Kelly E. , Bryan Margarette , Patel Prem S. , Rameshwar Pranela
Published: July 2006

Breast cancer cells (BCCs) show preference for the bone marrow (BM). An animal model showed 2 populations of BCCs in the BM with regard to their cycling states. An in vitro model of early BC entry into BM showed normal hematopoiesis. Here, we show a critical role for BCC-derived SDF-1α in hematopoietic regulation. The studies used a coculture of BM stroma and BCCs (cell lines and stage II BCCs). Northern blots and enzyme-linked immunosorbent assay (ELISA) showed gradual decreases in SDF-1α production in BCCs as they contact BM stroma, indicating partial microenvironmental effects caused by stroma on the BCCs. SDF-1 knock-down BCCs and increased exogenous SDF-1α prevented contact inhibition between BCCs and BM stroma. Contact inhibition was restored with low SDF-1α levels. Long-term culture-initiating assays with CD34+/CD38–/Lin– showed normal hematopoiesis provided that SDF-1α levels were reduced in BCCs. Gap junctions (connexin-43 [CX-43]) were formed between BCCs and BM stroma, with concomitant interaction between CD34+/CD38–/Lin– and BM stroma but not with the neighboring BCCs. In summary, SDF-1α levels are reduced in BCCs that contact BM stroma. The low levels of SDF-1α in BCCs regulate interactions between BM stroma and hematopoietic progenitors, consequently facilitating normal hematopoiesis.
G-protein–gated inwardly rectifying potassium channels regulate ADP-induced cPLA2 activity in platelets through Src family kinases
Authors: Shankar Haripriya , Kahner Bryan N. , Prabhakar Janani , Lakhani Parth , Kim Soochong , Kunapuli Satya P.
Published: July 2006

ADP-induced TXA2 generation requires the costimulation of P2Y1, P2Y12, and the GPIIb/IIIa receptors. Signaling events downstream of the P2Y receptors that contribute to ADP-induced TXA2 generation have not been clearly delineated. In this study, we have investigated the role of G-protein–gated inwardly rectifying potassium channels (GIRKs), a recently identified functional effector for the P2Y12 receptor, in the regulation of ADP-induced TXA2 generation. At 10-μM concentrations, the 2 structurally distinct GIRK channel blockers, SCH23390 and U50488H, caused complete inhibition of ADP-induced cPLA2 phosphorylation and TXA2 generation, without affecting the conversion of AA to TXA2 or ADP-induced primary platelet aggregation in aspirin-treated platelets. In addition, Src family kinase selective inhibitors abolished 2MeSADP-mediated cPLA2 phosphorylation and TXA2 generation. Furthermore, these GIRK channel blockers completely blocked Gi-mediated Src kinase activation, suggesting that GIRK channels are upstream of Src family tyrosine kinase activation. In weaver mouse platelets, which have dysfunctional GIRK2 subunits, ADP-induced TXA2 generation was impaired. However, we did not observe any defect in 2MeSADP-induced platelet functional responses in GIRK2-null mouse platelets, suggesting that functional channels composed of other GIRK subunits contribute to ADP-induced TXA2 generation, via the regulation of the Src and cPLA2 activity.
Stat1 and SUMO modification
Authors: Song Li , Bhattacharya Samita , Yunus Ali A. , Lima Christopher D. , Schindler Christian
Published: July 2006

Many proteins are known to undergo small ubiquitin-related modifier (SUMO) modification by an E1-, E2-, and E3-dependent ligation process. Recognition that protein inhibitor of activated signal transducers and activators of transcription (STATs) (PIAS) proteins are SUMO E3 ligases raised the possibility that STATs may also be regulated by SUMO modification. Consistent with this possibility, a SUMO-ylation consensus site (ΨKxE; Ψ indicates hydrophobic residue, and x indicates any residue) was identified in Stat1 (ie, 702IKTE705), but not in other STATs. Biochemical analysis confirmed that Stat1 K703 could be SUMO modified in vitro. Mutation of this critical lysine (ie, Stat1K703R) yielded a protein that, when expressed in Stat1–/– mouse embryonic fibroblasts (MEFs), exhibited enhanced DNA binding and nuclear retention. This was associated with modest changes in transcriptional and antiviral activity. However, mutation of the second critical residue in the SUMO consensus site, E705 (ie, Stat1E705A), yielded a protein with wild-type DNA binding, nuclear retention, and transcriptional and antiviral activity. Similar observations were made when these mutants were expressed in primary Stat1–/– macrophages. These observations suggest that although Stat1 can uniquely be SUMO-ylated in vitro, this modification is unlikely to play an important role in regulating Stat1 activity in vivo.
Transcriptional repression and DNA hypermethylation of a small set of ES cell marker genes in male germline stem cells
Authors: Imamura Masanori , Miura Kyoko , Iwabuchi Kumiko , Ichisaka Tomoko , Nakagawa Masato , Lee Jiyoung , Kanatsu-Shinohara Mito , Shinohara Takashi , Yamanaka Shinya
Published: July 2006

Background

We previously identified a set of genes called ECATs (ES cell-associated transcripts) that are expressed at high levels in mouse ES cells. Here, we examine the expression and DNA methylation of ECATs in somatic cells and germ cells.

Results

In all ECATs examined, the promoter region had low methylation levels in ES cells, but higher levels in somatic cells. In contrast, in spite of their lack of pluripotency, male germline stem (GS) cells expressed most ECATs and exhibited hypomethylation of ECAT promoter regions. We observed a similar hypomethylation of ECAT loci in adult testis and isolated sperm. Some ECATs were even less methylated in male germ cells than in ES cells. However, a few ECATs were not expressed in GS cells, and most of them targets of Oct3/4 and Sox2. The Octamer/Sox regulatory elements were hypermethylated in these genes. In addition, we found that GS cells express little Sox2 protein and low Oct3/4 protein despite abundant expression of their transcripts.

Conclusion

Our results suggest that DNA hypermethylation and transcriptional repression of a small set of ECATs, together with post-transcriptional repression of Oct3/4 and Sox2, contribute to the loss of pluripotency in male germ cells.
Analysis of bacteria-challenged wild silkmoth, Antheraea mylitta (lepidoptera) transcriptome reveals potential immune genes
Authors: Gandhe Archana S , Arunkumar K P , John Serene H , Nagaraju J
Published: July 2006

Background

In the recent years a strong resemblance has been observed between the insect immune system and the mammalian innate immune mechanisms suggesting their common origin. Among the insects, only the dipterans (Drosophila and various mosquito species) have been widely investigated for their immune responses towards diverse pathogens. In the present study we constructed and analysed the immune transcriptome of the lepidopteran Antheraea mylitta, an economically important Indian tasar silkmoth with a view to unravel the potential immune-related genes and pathways.

Results

An expressed sequence tag (EST) library was constructed from mRNA obtained from fat bodies of A. mylitta larvae that had been challenged by infection with Escherichia coli cells. We identified 719 unique ESTs from a total of 1412 sequences so generated. A third of the transcriptome showed similarity with previously characterized immune-related genes that included both the known and putative immune genes. Of the four putative novel defence proteins (DFPs) annotated by PSI-BLAST three showed similarity to extracellular matrix proteins from vertebrates implicated in innate immunity, while the fourth was similar to, yet distinct from, the anti-microbial protein cecropin. Finally, we analysed the expression profiles of 15 potential immune-related genes, and the majority of them were induced more prominently with E. coli compared to Micrococcus luteus. We also identified several unknown proteins, some of which could have probable immune-related functions based on the results of the ProDom analysis.

Conclusion

The present study has identified many potential immune-related genes in A. mylitta some of which are vertebrate homologues and others are hitherto unreported putative defence proteins. Several genes were present as members of gene families, as has also been observed in other insect species.
Lymph node hemophagocytosis in rickettsial diseases: a pathogenetic role for CD8 T lymphocytes in human monocytic ehrlichiosis (HME)?
Authors: Dierberg Kerry L , Dumler J Stephen
Published: July 2006

Background

Human monocytic ehrlichiosis (HME) and Rocky Mountain spotted fever (RMSF) are caused by Ehrlichia chaffeensis and Rickettsia rickettsii, respectively. The pathogenesis of RMSF relates to rickettsia-mediated vascular injury, but it is unclear in HME.

Methods

To study histopathologic responses in the lymphatic system for correlates of immune injury, lymph nodes from patients with HME (n = 6) and RMSF (n = 5) were examined. H&E-stained lymph node tissues were examined for five histopathologic features, including hemophagocytosis, cellularity, necrosis, and vascular congestion and edema. The relative proportions of CD68 macrophages, CD8 and CD4 T lymphocytes, and CD20 B lymphocytes were evaluated by immunohistochemical staining.

Results

Hemophagocytosis was similar in HME and RMSF, and was greater than in control cases (p = .015). Cellularity in HME was not different from controls, whereas RMSF lymph nodes were markedly less cellular (p < 0.002). E. chaffeensis-infected mononuclear phagocytes were infrequent compared to R. rickettsii-infected endothelial cells. More CD8 cells in lymph nodes were observed with HME (p < .001), but no quantitative differences in CD4 lymphocytes, macrophages, or B lymphocytes were identified.

Conclusion

Hemophagocytosis, CD8 T cell expansion, and the paucity of infected cells in HME, suggest that E. chaffeensis infection leads to macrophage activation and immune-mediated injury.
Similar folds with different stabilization mechanisms: the cases of prion and doppel proteins
Authors: Colacino Stefano , Tiana Guido , Colombo Giorgio
Published: July 2006

Background

Protein misfolding is the main cause of a group of fatal neurodegenerative diseases in humans and animals. In particular, in Prion-related diseases the normal cellular form of the Prion Protein PrP (PrP

C
) is converted into the infectious PrP

Sc
through a conformational process during which it acquires a high β-sheet content. Doppel is a protein that shares a similar native fold, but lacks the scrapie isoform. Understanding the molecular determinants of these different behaviours is important both for biomedical and biophysical research.

Results

In this paper, the dynamical and energetic properties of the two proteins in solution is comparatively analyzed by means of long time scale explicit solvent, all-atom molecular dynamics in different temperature conditions. The trajectories are analyzed by means of a recently introduced energy decomposition approach (Tiana et al, Prot. Sci. 2004) aimed at identifying the key residues for the stabilization and folding of the protein. Our analysis shows that Prion and Doppel have two different cores stabilizing the native state and that the relative contribution of the nucleus to the global stability of the protein for Doppel is sensitively higher than for PrP. Moreover, under misfolding conditions the Doppel core is conserved, while the energy stabilization network of PrP is disrupted.

Conclusion

These observations suggest that different sequences can share similar native topology with different stabilizing interactions and that the sequences of the Prion and Doppel proteins may have diverged under different evolutionary constraints resulting in different folding and stabilization mechanisms.
Childhood asthma and indoor allergens in Native Americans in New York
Authors: Surdu Simona , Montoya Lupita D , Tarbell Alice , Carpenter David O
Published: July 2006

Background

The objective of this study was to assess the correlation between childhood asthma and potential risk factors, especially exposure to indoor allergens, in a Native American population.

Methods

A case-control study of St. Regis Mohawk tribe children ages 2–14 years, 25 diagnosed with asthma and 25 controls was conducted. Exposure was assessed based on a personal interview and measurement of mite and cat allergens (Der p 1, Fel d 1) in indoor dust.

Results

A non-significant increased risk of childhood asthma was associated with self-reported family history of asthma, childhood environmental tobacco smoke exposure, and air pollution. There was a significant protective effect of breastfeeding against current asthma in children less than 14 years (5.2 fold lower risk). About 80% of dust mite and 15% of cat allergen samples were above the threshold values for sensitization of 2 and 1 μg/g, respectively. The association between current asthma and exposure to dust mite and cat allergens was positive but not statistically significant.

Conclusion

This research identified several potential indoor and outdoor risk factors for asthma in Mohawks homes, of which avoidance may reduce or delay the development of asthma in susceptible individuals.
Colour duplex sonography of temporal arteries before decision for biopsy: a prospective study in 55 patients with suspected giant cell arteritis
Authors: Karahaliou Maria , Vaiopoulos George , Papaspyrou Spiros , Kanakis Meletios A , Revenas Konstantinos , Sfikakis Petros P
Published: July 2006

Although a temporal artery biopsy is the gold standard for the diagnosis of giant cell arteritis (GCA), there is considerable evidence that characteristic signs demonstrated by colour duplex sonography (CDS) of the temporal arteries may be of diagnostic importance. We aimed to test the hypothesis that CDS can replace biopsy in the algorithm for the approach to diagnose GCA. Bilateral CDS was performed in consecutive patients older than 50 years with clinically suspected GCA, as well as in 15 age- and gender-matched control subjects with diabetes mellitus and/or stroke and 15 healthy subjects, to assess flow parameters and the possible presence of a dark halo around the arterial lumen. Unilateral temporal artery biopsy was then performed in patients with suspected GCA, which was directed to a particular arterial segment in case a halo was detected in CDS. Final diagnoses, after completion of a 3-month follow-up in 55 patients, included GCA (n = 22), polymyalgia rheumatica (n = 12), polyarteritis nodosa, Wegener's, and Adamantiades-Behçet's diseases (n = 3), and neoplastic (n = 8) and infectious diseases (n = 10). A dark halo of variable size (0.7–2.0 mm) around the vessel lumen was evident at baseline CDS in 21 patients (in 12 and 9 uni- or bilaterally, respectively) but in none of the controls. The presence of unilateral halo alone yielded 82% sensitivity and 91% specificity for GCA, whereas the specificity reached 100% when halos were found bilaterally. Blood-flow abnormal parameters (temporal artery diameter, peak systolic blood-flow velocities, stenoses, occlusions) were common in GCA and non-GCA patients, as well as in healthy and atherosclerotic disease-control, elderly subjects. At follow-up CDS examinations performed at 2 and 4 weeks after initiation of corticosteroid treatment for GCA, halos disappeared in all 18 patients (9 and 9, respectively). We conclude that CDS, an inexpensive, non-invasive, and easy-to-perform method, allows a directional biopsy that has an increased probability to confirm the clinical diagnosis. Biopsy is not necessary in a substantial proportion of patients in whom bilateral halo signs can be found by CDS.
Association of the FCRL3gene with rheumatoid arthritis: a further example of population specificity?
Authors: Eyre Stephen , Bowes John , Potter Catherine , Worthington Jane , Barton Anne
Published: July 2006

Association of a functional promoter polymorphism mapping to the Fc receptor-like 3 (FCRL3) gene has recently been reported and replicated with rheumatoid arthritis (RA) in Japanese populations. The aim of this study was to investigate association of the FCRL3 gene with RA in UK subjects. DNA was available from 1065 patients with RA and 2073 population controls from the UK. Four single nucleotide polymorphism (SNP) markers (FCRL3-169*C/T (fclr3_3, rs7528684), fclr3_4 (rs11264799), fclr3_5 (rs945635), fclr3_6 (rs3761959)) all previously associated with RA in a Japanese population were genotyped in 761 RA samples and 484 controls. In the remaining samples, only the putative disease causal polymorphism, FCRL3-169*C/T, was tested. Genotyping was performed using either the Sequenom MassArray iPlex platform or a 5' Allelic discrimination assay (Taqman, ABI). Extensive linkage disequilibrium was present across the promoter SNPs genotyped (r2 values = 0.60-0.98). Allele frequencies did not differ between RA cases and controls either for the putative disease causal polymorphism (odds ratio FCRL3-169*C allele = 0.97 (0.87-1.07), p = 0.51) or for the other SNPs tested. Similarly, no association was detected with RA using haplotype analysis or when stratification by shared epitope carriage or by presence of rheumatoid factor was undertaken. This study was powered to detect an effect size of 1.24 or greater for the FCRL3-169*C/T functional promoter polymorphism but no evidence for association was detected, suggesting that this gene will not have a substantial effect in determining susceptibility to RA in populations of Northern European descent.
Diagnostic value of anti-human citrullinated fibrinogen ELISA and comparison with four other anti-citrullinated protein assays
Authors: Vander Cruyssen Bert , Cantaert Tineke , Nogueira Leonor , Clavel Cyril , De Rycke Leen , Dendoven Amélie , Sebag Mireille , Deforce Dieter , Vincent Christian , Elewaut Dirk , Serre Guy , De Keyser Filip
Published: July 2006

We studied the diagnostic performance of the anti-human citrullinated fibrinogen antibody (AhFibA) ELISA for rheumatoid arthritis (RA) in a consecutive cohort (population 1) and evaluated the agreement between the AhFibA ELISA and four other assays for anti-citrullinated protein/peptide antibodies (ACPAs) as well as rheumatoid factor in patients with longstanding RA (population 2). Population 1 consisted of 1024 patients with rheumatic symptoms; serum samples from these patients were sent to our laboratory for ACPA testing within the context of a diagnostic investigation for RA. Ninety-two of these patients were classified as having RA according to the American College of Rheumatology criteria and 463 were classified as non-RA patients. Population 2 consisted of 180 patients with longstanding RA and was used to assess agreement and correlations between five ACPA assays: anti-cyclic citrullinated peptide (CCP)1 and anti-CCP2 antibodies were detected using a commercially available ELISA, AhFibA using ELISA, and anti-PepA and anti-PepB antibodies using line immunoassay. Applying previously proposed cut-offs for AhFibA, we obtained a sensitivity of 60.9% and a specificity of 98.7% in population 1. Receiver operating characteristic curve analysis could not detect a significant difference in diagnostic performance between the AhFibA ELISA and anti-CCP2 assay. Performing a hierarchical nearest neighborhood cluster analysis of the five different ACPA assays in population 2, we identified two clusters: a cluster of anti-pepA, anti-pepB and anti-CCP1, and a cluster of AhFibA and anti-CCP2. In conclusion, we found that AhFibA and anti-CCP2 antibodies had similar diagnostic performance. However, disagreement between ACPA tests may occur.
Hepatocyte growth factor prevents lupus nephritis in a murine lupus model of chronic graft-versus-host disease
Authors: Kuroiwa Takanori , Iwasaki Tsuyoshi , Imado Takehito , Sekiguchi Masahiro , Fujimoto Jiro , Sano Hajime
Published: July 2006

Chronic graft-versus-host disease (GVHD) induced in (C57BL/6 × DBA/2) F1 (BDF1) mice by the injection of DBA/2 mouse spleen cells represents histopathological changes associated with systemic lupus erythematosus (SLE), primary biliary cirrhosis (PBC) and Sjogren's syndrome (SS), as indicated by glomerulonephritis, lymphocyte infiltration into the periportal area of the liver and salivary glands. We determined the therapeutic effect of hepatocyte growth factor (HGF) gene transfection on lupus using this chronic GVHD model. Chronic GVHD mice were injected in the gluteal muscle with either HVJ liposomes containing 8 μg of the human HGF expression vector (HGF-HVJ liposomes) or mock vector (untreated control). Gene transfer was repeated at 2-week intervals during 12 weeks. HGF gene transfection effectively prevented the proteinuria and histopathological changes associated with glomerulonephritis. While liver and salivary gland sections from untreated GVHD mice showed prominent PBC- and SS-like changes, HGF gene transfection reduced these histopathological changes. HGF gene transfection greatly reduced the number of splenic B cells, host B cell major histocompatibility complex class II expression, and serum levels of IgG and anti-DNA antibodies. IL-4 mRNA expression in the spleen, liver, and kidneys was significantly decreased by HGF gene transfection. CD28 expression on DBA/2 CD4+ T cells was decreased by the addition of recombinant HGF in vitro. Furthermore, IL-4 production by DBA/2 CD4+ T cells stimulated by irradiated BDF1 dendritic cells was significantly inhibited by the addition of recombinant HGF in vitro. These results suggest that HGF gene transfection inhibited T helper 2 immune responses and reduced lupus nephritis, autoimmune sialoadenitis, and cholangitis in chronic GVHD mice. HGF may represent a novel strategy for the treatment of SLE, SS and PBC.
Expression profiling of metalloproteinases and their inhibitors in synovium and cartilage
Authors: Davidson Rose K , Waters Jasmine G , Kevorkian Lara , Darrah Clare , Cooper Adele , Donell Simon T , Clark Ian M
Published: July 2006

Cartilage destruction in osteoarthritis (OA) is thought to be mediated by two main enzyme families; the matrix metalloproteinases (MMPs) are responsible for cartilage collagen breakdown, whereas enzymes from the 'a disintegrin and metalloproteinase domain with thrombospondin motifs' (ADAMTS) family mediate cartilage aggrecan loss. Tissue inhibitors of metalloproteinases (TIMPs) regulate the activity of these enzymes. Although cartilage destruction in OA might be driven by the chondrocyte, low-grade synovitis is reported in patients with all grades of this disease.

Our earlier work profiling these gene families in cartilage identified a number of genes that are regulated in OA, which are hence implicated in the disease process. Because the synovium might contribute to cartilage-matrix destruction in OA, we have extended the screening in the current study. We have profiled MMP, ADAMTS and TIMP genes in both cartilage and synovium from patients with either OA of the hip or a fracture to the neck of femur (NOF), giving a more complete picture of proteolysis in this disease.

The four most significantly upregulated genes (P < 0.0001) in OA synovium compared to the fractured NOF are MMP28, ADAMTS16, ADAMTS17 and TIMP2. For MMP9, MMP10, MMP12, MMP17, MMP23, MMP28, ADAMTS4, and ADAMTS9, there is a significant correlation between expression levels in the synovium and cartilage, suggesting similar mechanisms of regulation. Additionally, we have shown that in cartilage the median level of steady-state mRNA for MMP13 is approximately 20-fold higher than MMP28 and approximately 1,500-fold higher than ADAMTS16, with expression of this latter gene approximately 150-fold higher in synovium than cartilage.

This study is the most comprehensive analysis of the metzincin family of proteinases in the joint to date and has identified several proteinase genes not previously reported to be expressed or regulated in synovium.
Induction of tumour necrosis factor receptor-expressing macrophages by interleukin-10 and macrophage colony-stimulating factor in rheumatoid arthritis
Authors: Takasugi Koji , Yamamura Masahiro , Iwahashi Mitsuhiro , Otsuka Fumio , Yamana Jiro , Sunahori Katsue , Kawashima Masanori , Yamada Masao , Makino Hirofumi
Published: July 2006

Despite its potent ability to inhibit proinflammatory cytokine synthesis, interleukin (IL)-10 has a marginal clinical effect in rheumatoid arthritis (RA) patients. Recent evidence suggests that IL-10 induces monocyte/macrophage maturation in cooperation with macrophage-colony stimulating factor (M-CSF). In the present study, we found that the inducible subunit of the IL-10 receptor (IL-10R), type 1 IL-10R (IL-10R1), was expressed at higher levels on monocytes in RA than in healthy controls, in association with disease activity, while their expression of both type 1 and 2 tumour necrosis factor receptors (TNFR1/2) was not increased. The expression of IL-10R1 but not IL-10R2 was augmented on monocytes cultured in the presence of RA synovial tissue (ST) cell culture supernatants. Cell surface expression of TNFR1/2 expression on monocytes was induced by IL-10, and more efficiently in combination with M-CSF. Two-color immunofluorescence labeling of RA ST samples showed an intensive coexpression of IL-10R1, TNFR1/2, and M-CSF receptor in CD68+ lining macrophages. Adhered monocytes, after 3-day preincubation with IL-10 and M-CSF, could produce more IL-1β and IL-6 in response to TNF-α in the presence of dibutyryl cAMP, as compared with the cells preincubated with or without IL-10 or M-CSF alone. Microarray analysis of gene expression revealed that IL-10 activated various genes essential for macrophage functions, including other members of the TNFR superfamily, receptors for chemokines and growth factors, Toll-like receptors, and TNFR-associated signaling molecules. These results suggest that IL-10 may contribute to the inflammatory process by facilitating monocyte differentiation into TNF-α-responsive macrophages in the presence of M-CSF in RA.
Osteoarthritis and nutrition. From nutraceuticals to functional foods: a systematic review of the scientific evidence
Authors: Ameye Laurent G , Chee Winnie SS
Published: July 2006

The scientific and medical community remains skeptical regarding the efficacy of nutrition for osteoarthritis despite their broad acceptation by patients. In this context, this paper systematically reviews human clinical trials evaluating the effects of nutritional compounds on osteoarthritis. We searched the Medline, Embase, and Biosis databases from their inception to September 2005 using the terms random, double-blind method, trial, study, placebo, and osteoarthritis. We selected all peer-reviewed articles reporting the results of randomised human clinical trials (RCTs) in osteoarthritis that investigated the effects of oral interventions based on natural molecules. Studies on glucosamine and chondroitin sulfate were excluded. The quality of the RCTs was assessed with an osteoarthritic-specific standardised set of 12 criteria and a validated instrument. A best-evidence synthesis was used to categorise the scientific evidence behind each nutritional compound as good, moderate, or limited. A summary of the most relevant in vitro and animal studies is used to shed light on the potential mechanisms of action. Inclusion criteria were met by 53 RCTs out of the 2,026 identified studies. Good evidence was found for avocado soybean unsaponifiables. Moderate evidence was found for methylsulfonylmethane and SKI306X, a cocktail of plant extracts. Limited evidence was found for the Chinese plant extract Duhuo Jisheng Wan, cetyl myristoleate, lipids from green-lipped mussels, and plant extracts from Harpagophytum procumbens. Overall, scientific evidence exists for some specific nutritional interventions to provide symptom relief to osteoarthritic patients. It remains to be investigated whether nutritional compounds can have structure-modifying effects.
Breast cancer prognosis by combinatorial analysis of gene expression data
Authors: Alexe Gabriela , Alexe Sorin , Axelrod David E , Bonates Tibérius O , Lozina Irina I , Reiss Michael , Hammer Peter L
Published: July 2006

Introduction

The potential of applying data analysis tools to microarray data for diagnosis and prognosis is illustrated on the recent breast cancer dataset of van 't Veer and coworkers. We re-examine that dataset using the novel technique of logical analysis of data (LAD), with the double objective of discovering patterns characteristic for cases with good or poor outcome, using them for accurate and justifiable predictions; and deriving novel information about the role of genes, the existence of special classes of cases, and other factors.

Method

Data were analyzed using the combinatorics and optimization-based method of LAD, recently shown to provide highly accurate diagnostic and prognostic systems in cardiology, cancer proteomics, hematology, pulmonology, and other disciplines.

Results

LAD identified a subset of 17 of the 25,000 genes, capable of fully distinguishing between patients with poor, respectively good prognoses. An extensive list of 'patterns' or 'combinatorial biomarkers' (that is, combinations of genes and limitations on their expression levels) was generated, and 40 patterns were used to create a prognostic system, shown to have 100% and 92.9% weighted accuracy on the training and test sets, respectively. The prognostic system uses fewer genes than other methods, and has similar or better accuracy than those reported in other studies. Out of the 17 genes identified by LAD, three (respectively, five) were shown to play a significant role in determining poor (respectively, good) prognosis. Two new classes of patients (described by similar sets of covering patterns, gene expression ranges, and clinical features) were discovered. As a by-product of the study, it is shown that the training and the test sets of van 't Veer have differing characteristics.

Conclusion

The study shows that LAD provides an accurate and fully explanatory prognostic system for breast cancer using genomic data (that is, a system that, in addition to predicting good or poor prognosis, provides an individualized explanation of the reasons for that prognosis for each patient). Moreover, the LAD model provides valuable insights into the roles of individual and combinatorial biomarkers, allows the discovery of new classes of patients, and generates a vast library of biomedical research hypotheses.
Reproductive factors and breast cancer risk according to joint estrogen and progesterone receptor status: a meta-analysis of epidemiological studies
Authors: Ma Huiyan , Bernstein Leslie , Pike Malcolm C , Ursin Giske
Published: July 2006

Introduction

Although reproductive factors have been known for decades to be associated with breast cancer risk, it is unclear to what extent these associations differ by estrogen and progesterone receptor (ER/PR) status. This report presents the first meta-analysis of results from epidemiological studies that have investigated parity, age at first birth, breastfeeding, and age at menarche in relation to ER+PR+ and ER-PR- cancer risk.

Materials and methods

We calculated summary relative risks (RRs) and corresponding 95% confidence intervals (CIs) using a fixed effects model.

Results

Each birth reduced the risk of ER+PR+ cancer by 11% (RR per birth = 0.89, 95% CI = 0.84–0.94), and women who were in the highest age at first birth category had, on average, 27% higher risk of ER+PR+ cancer compared with women who were in the youngest age at first birth category (RR = 1.27, 95% CI = 1.07–1.50). Neither parity nor age at first birth was associated with the risk of ER-PR- cancer (RR per birth = 0.99, 95% CI = 0.94–1.05; RR of oldest versus youngest age at first birth category = 1.01, 95% CI = 0.85–1.20). Breastfeeding and late age at menarche decreased the risk of both receptor subtypes of breast cancer. The protective effect of late age at menarche was statistically significantly greater for ER+PR+ than ER-PR- cancer (RR = 0.72 for ER+PR+ cancer; RR = 0.84 for ER-PR- cancer, p for homogeneity = 0.006).

Conclusion

Our findings suggest that breastfeeding (and age at menarche) may act through different hormonal mechanisms than do parity and age at first birth.