bluuebunny/crossref_metadata_2025 huggingface dataset:
Ankle—brachial index and hemostatic markers in the Atherosclerosis Risk in Communities (ARIC) study cohort
Authors: Reich Laura M. , Heiss Gerardo , Boland Lori L. , Hirsch Alan T. , Wu Kenneth , Folsom Aaron R.
Published: November 2007

To determine whether elevated levels of hemostatic and inflammatory markers [von Willebrand factor (vWF), fibrinogen, D-dimer, factor VII, factor VIII, PAI-1, tPA, beta-thromboglobulin (β-TG), CRP, and WBC count] are associated with increased peripheral arterial disease (PAD) prevalence, measured by low ABI, we studied 13,778 participants from the ARIC study in a cross-sectional analysis after adjustment for major cardiovascular risk factors. PAD was positively associated with fibrinogen, vWF, factor VIII, WBC count, D-dimer, β-TG, and CRP (p for trend <0.05) but not with the other markers. Adjusted odds ratios for the highest versus the lowest quartile of fibrinogen in men and women, respectively, were 3.49 (95% CI 1.68—7.26) and 2.44 (95% CI 1.58—3.77); for vWF 2.36 (95% CI 1.36—4.07) and 1.45 (95% CI 1.00—2.10); for factor VIII 2.31 (95% CI 1.36—3.94) and 1.68 (95% CI 1.14—2.48). In a smaller subset, the sex and risk factor adjusted odds ratio for the highest versus the lowest quartile of D-dimer was 2.70 (95% CI 1.56—4.65), for β-TG was 1.80 (95% CI 1.12—2.88), and for CRP was 1.57 (95% CI 0.84—2.95). Plasma levels of hemostatic and inflammatory markers are elevated in PAD, suggesting these processes are involved in the pathophysiology of PAD.
Contrast-enhanced ultrasound imaging of atherosclerotic carotid plaque neovascularization: a new surrogate marker of atherosclerosis?
Authors: Shah Falak , Balan Prakash , Weinberg Matthew , Reddy Vijaya , Neems Rachel , Feinstein Matthew , Dainauskas John , Meyer Peter , Goldin Marshall , Feinstein Steven B.
Published: November 2007

An atherosclerotic plaque requires a nutrient blood supply, which is predominantly derived from arterial vasa vasorum. A variety of factors (environmental and genetic) contribute to the initiation and growth of atherosclerosis within vessel walls. Chemotactic factors, such as tissue ischemic and hypoxic factors, stimulate the release of vascular endothelial growth factor (VEGF) proteins, resulting in vessel wall angiogenesis. These developments often precede the formation of the luminal plaque. In this report, we describe the use of contrast-enhanced carotid ultrasound (CECU) imaging for the detection and quantification of intra-plaque neovascularization. The efficacy of CECU was measured against the neovascular density observed within the tissue specimens obtained at the time of carotid endarterectomy surgery. The objective of this study was to provide a histologic correlation between CECU and carotid artery atherosclerotic plaque neovascularization. Fifteen patients with significant atherosclerotic carotid artery disease received a CECU examination prior to undergoing a carotid endarterectomy (CEA). Two patients received bilateral endarterectomies, resulting in a total of 17 cases. At the time of surgery, carotid plaque samples were surgically removed and stained with specific vascular markers (CD31, CD34, von Willebrand factor, and hemosiderin) designed to identify the presence and degree of neovascularization. The intra-plaque neovascularization recorded on preoperative CECU was correlated with the degree of neovascularization noted in the tissue specimens. The CECU neovascularization was correlated to CD31-stained tissue specimens. This correlation value was 0.68 using Spearman's rank method. When CECU results were correlated with the other histologic markers (CD34, von Willebrand factor, and hemosiderin), a correlation of 0.50 was obtained. In conclusion, contrast-enhanced carotid ultrasound correlated to the presence and degree of intra-plaque neovascularization as determined from histology specimens.
Arterial aging: pathophysiological principles
Authors: O'Rourke Michael F.
Published: November 2007

In the nineteenth century, prior to the introduction of the cuff sphygmomanometer, arteriosclerosis (stiffening of arteries) was recognized by clinicians and by life insurance companies as an indicator of vascular aging and cardiovascular risk, even in asymptomatic individuals. Through the twentieth century, views on aging came to focus on values of systolic and diastolic pressure and on obstructive atherosclerotic disease. Such focus deflected attention from the primary aging change which occurs in all societies, and is represented by stiffening and dilation of the proximal aorta. This review emphasizes the cushioning function of elastic arteries — principally the aorta — and how in youth this results in optimal interaction with the heart, and optimal steady flow through peripheral resistance vessels. Aortic stiffening with age is principally due to fatigue and fracture of elastin lamellae, with transfer of stress to stiffer collagenous components. Stiffening increases left ventricular load and myocardial blood requirement, but limits the capacity for blood supply during diastole. Consequences are cardiac failure and predisposition to ischaemia. The second, under-appreciated effect of aortic stiffening is transmission of flow pulsations downstream into vasodilated organs, principally brain and kidney, where pulsatile energy is dissipated and fragile microvessels are damaged. This accounts for micro infarcts and microhaemorrhages, with specialized cell damage, cognitive decline and renal failure. The aging process can be best monitored by change in the arterial pressure wave rather than by reliance on the cuff sphygmomanometer. This reintroduces the approaches by clinicians and life insurance examiners of the nineteenth century, endorses modern treatments for established disease, and holds the promise of detecting premature arterial degeneration, and better applying lifestyle measures and vasoactive medications to modify the aging process.
Increased levels of apoptosis in gastrocnemius skeletal muscle in patients with peripheral arterial disease
Authors: Mitchell Robert G. , Duscha Brian D. , Robbins Jennifer L. , Redfern Shelley I. , Chung Jayer , Bensimhon Daniel R. , Kraus William E. , Hiatt William R. , Regensteiner Judith G. , Annex Brian H.
Published: November 2007

Intermittent claudication (IC) is the major clinical manifestation of peripheral arterial disease (PAD). Apoptosis has been linked to skeletal muscle pathophysiology in other chronic diseases such as congestive heart failure. This study tested the hypothesis that there would be increased levels of apoptosis in the skeletal muscle of patients with PAD compared with control individuals. In total, 26 individuals with PAD and 28 age-appropriate controls underwent studies of peak oxygen consumption (peak VO2) and a gastrocnemius muscle biopsy in the most symptomatic leg. Muscle biopsies were analyzed for apoptosis and caspase-3 activity. Patients with PAD had a reduced peak VO2 compared with controls. Apoptosis was increased in those with PAD compared with age-appropriate controls (3.83% ± 2.6 vs 1.53% ± 0.96; p < 0.001). In conclusion, PAD is associated with increased levels of apoptosis in the peripheral skeletal muscle. Further study is required to ascertain whether apoptosis plays a role in decreased functional capacity.
Imagining Intergroup Contact Can Improve Intergroup Attitudes
Authors: Turner Rhiannon N. , Crisp Richard J. , Lambert Emily
Published: November 2007

We investigated whether simply imagining contact with outgroup members can improve intergroup attitudes. In Experiment 1, young participants who imagined talking to an elderly person subsequently showed lower levels of intergroup bias than participants who imagined an outdoor scene. In Experiment 2, young participants who imagined talking to an elderly person subsequently showed lower levels of intergroup bias than participants who simply thought about elderly people, ruling out a priming explanation for our findings. In Experiment 3, heterosexual men who imagined talking to a homosexual man subsequently evaluated homosexual men more positively, perceived there to be greater variability among them, and experienced less intergroup anxiety compared to a control group. The effect of imagined contact on outgroup evaluations was mediated by reduced intergroup anxiety. These findings suggest that imagining intergroup contact could represent a viable alternative for reducing prejudice where actual contact between groups is impractical.
The Role of Heterosexual Identity Threat in Differential Support for Same-Sex `Civil Unions' versus `Marriages'
Authors: Schmitt Michael T. , Lehmiller Justin J. , Walsh Allison L.
Published: November 2007

Although US citizens generally oppose the legal recognition of same-sex marriages more than civil unions, the reasons for this opposition remain unclear. In two experiments, we presented participants with one of two hypothetical state laws legally recognizing same-sex partnerships. The laws differed only in the label applied to those partnerships (i.e. civil union or marriage). Across both studies, participants expressed less support for same-sex marriages relative to civil unions. In addition, participants considering the marriage law found it more threatening to heterosexuals' rights and social status than did those reading the civil union law, and this threat partially mediated the effect of the relationship label on support for the law. Thus, consistent with social identity theory, opposition to the same-sex marriage label is, in part, due to perceived threats to heterosexual identity.
Superordinate and Subgroup Identification as Predictors of Intergroup Evaluation in Common Ingroup Contexts
Authors: Stone Catriona H. , Crisp Richard J.
Published: November 2007

We examined the combined effects of subgroup and superordinate group identification on intergroup evaluations within common ingroup identity contexts. In Studies 1 and 2 we observed a positive correlation between subgroup identification and intergroup bias, and a negative correlation between superordinate identification and bias. In Study 3 we replicated these effects using alternative measures and observed a common path underlying these relationships: the perceived psychological distance between the self and outgroup. In Studies 4 and 5 we replicated this path model and found that the relationship between superordinate identification and intergroup bias was contingent upon making the superordinate identity salient, but this was not the case for subgroup identification. We discuss the findings in the context of theoretical and applied development of the Common Ingroup Identity Model.
Stereotypes as Shared Beliefs: Effects of Group Identity on Dyadic Conversations
Authors: Karasawa Minoru , Asai Nobuko , Tanabe Yoshiko
Published: November 2007

Two experiments examined the influence of stereotypes on dyadic conversations. Undergraduate students listened to a recorded interview of a student who was described as either a member of their in-group or of an out-group. The interview contained stereotype-consistent (SC) and stereotype-inconsistent (SI) descriptions of each group. Participants' conversations about the stimulus person were content-analyzed. One most consistent result was that for the out-group target, participants made more SI than SC utterances and spent more time discussing SI information. The difference between SC and SI utterances disappeared (Study 2) or was reversed (Study 1) for the in-group target. These patterns were observed particularly when the stimulus information contained a balanced combination of SC and SI characteristics. Furthermore, the stereotypicality of the conversations was related not only to the participant's own judgments but also to the partner's judgments. The significance of studying stereotypes as collectively shared intergroup attitudes is discussed.
Multicultural and Colorblind Ideology, Stereotypes, and Ethnocentrism among Black and White Americans
Authors: Ryan Carey S. , Hunt Jennifer S. , Weible Joshua A. , Peterson Charles R. , Casas Juan F.
Published: November 2007

We examined Blacks' and Whites' perceptions of group variability and positivity as well as their beliefs about the extent to which multiculturalism and colorblindness would improve intergroup relations. In two studies, responses to questionnaires indicated that the tendency to endorse multiculturalism more than colorblindness was greater among Blacks than Whites; Blacks consistently endorsed multiculturalism more than colorblindness and Whites endorsed colorblindness more than did Blacks. Both studies also revealed evidence of out-group homogeneity and ethnocentrism. Stronger endorsement of multiculturalism relative to colorblindness predicted stronger stereotypes among Blacks, whereas stronger endorsement of colorblindness relative to multiculturalism predicted stronger stereotypes among Whites. In Study 2, stronger endorsement of multiculturalism relative to colorblindness predicted less ethnocentrism; this relationship did not depend on ethnicity.
Social Categories and Group Preference Disputes: The Aversion to Winner-Take-All Solutions
Authors: Garcia Stephen M. , Miller Dale T.
Published: November 2007

Six studies explored the hypothesis that third parties are averse to resolving preference disputes with winner-take-all solutions when disputing factions belong to different social categories (e.g. gender, nationality, firms, etc.) versus the same social category. Studies 1—3 showed that third parties' aversion to winner-take-all solutions, even when they are based on the unbiased toss of a coin, is greater when the disputed preferences correlate with social category membership than when they do not. Studies 4—6 suggested that reluctance to resolve inter-category disputes in a winner-take-all manner is motivated by a desire to minimize the affective disparity—the hedonic gap—between the winning and losing sides. The implication is that winner-take-all outcomes, even those that satisfy conditions of procedural fairness, become unacceptable when disputed preferences cleave along social category lines.
Arrest as punishment
Authors: Yanyou Yi
Published: November 2007

In analyzing the law concerning arrest, this article demonstrates that even though China's law of criminal procedure prescribes strict requirements, these legal prescriptions are not strictly upheld in practice. The abuse of arrests is common. Most notably, the use of arrest as punishment is the primary form of abuse inflicted by law enforcement. Reasons for such abuse include misunderstandings of the law, the prevalence of crime-control oriented values, and flaws in checks-and-balances mechanisms. Reduction of such abuses will entail a proper understanding of the law, the achievement of gradual ideological change, and the step-by-step reestablishment of checks and balances.
Japanese criminal justice
Authors: Hamai Koichi , Ellis Thomas
Published: November 2007

Despite its post-war reputation as one of the most crime-free industrialized countries Japan has a rapidly increasing recorded crime rate and corresponding falling clearance rate in police statistics. In 1998, only 19 per cent of the Japanese public thought crime was getting worse, but by 2005 this had increased to 48 per cent. The first part of this article, therefore, examines statistical records to assess the public's perception of increasing crime. Recent evidence (Hamai and Ellis, 2006), summarised here, shows that in the late 1990s, press coverage of police scandals provoked key policing policy changes. These changes resulted in a sudden drastic increase in recorded crime, due to the increase in hitherto unreported and less serious forms of crime, and a coincident dramatic decrease in clearance rates. The second part of the article then examines, in more depth, how the myth of the collapse of secure society was created and has been maintained. The main focus is on the inaccurate media coverage of crime and the growing influence of the victims' movement. The article then considers the impact of increasing punitivism along with an analysis of changes in the prison population.
Race, Gender, and Legal Counsel
Authors: Guevara Lori , Herz Denise , Spohn Cassia
Published: November 2007

This study examines the influence of race, gender, and type of legal counsel on juvenile court outcomes. Data from a sample of juvenile court referrals from two midwestern juvenile courts indicate that the effect of these factors varied by court location. The severity or leniency of the disposition outcome was determined by race, gender, type of legal counsel, and court location. This study clearly demonstrates the need for an approach that considers the interplay between legally relevant and legally irrelevant factors on juvenile justice decision making.
Animals, Empathy, and Violence
Authors: Sprinkle Julie E.
Published: November 2007

This study evaluates the effectiveness of a school-based violence prevention/intervention and character education program that uses rescued shelter dogs to teach antiviolence and prosocial messages to elementary and middle school students. This study uses student self-report, disciplinary data, and teacher observational data to measure violent and aggressive behaviors, beliefs about aggression, and levels of empathy in program participants before and after exposure to the program's curriculum. Findings indicate that receiving the program significantly alters students' normative beliefs about aggression, levels of empathy, and displays of violent and aggressive behaviors.
Examining the Influence of Matza's Principles of Justice and Their Impact on Reverse Waiver Decisions
Authors: Burrow John D.
Published: November 2007

During the last decade, a number of studies have presented a mixed picture regarding the efficacy of transfer to adult court. A focus on legal and secondary legal factors have shed a considerable amount of light on transfer decisions; however, little is known about the factors that judges consider when they use reverse waiver to keep offenders under juvenile court jurisdiction. Using a sample of 530 offenders who were transferred to adult court (direct file), this study uses Matza's principles of justice as a framework for understanding the sentencing decisions of judges who use their sentencing power to reverse waive offenders back to juvenile court. Findings suggest that extralegal factors such as offense location and personal characteristics of judges may play an important role in the decision-making process.
Decoupling of arsenic and iron release from ferrihydrite suspension under reducing conditions: a biogeochemical model
Authors: Burnol André , Garrido Francis , Baranger Philippe , Joulian Catherine , Dictor Marie-Christine , Bodénan Françoise , Morin Guillaume , Charlet Laurent
Published: November 2007

High levels of arsenic in groundwater and drinking water are a major health problem. Although the processes controlling the release of As are still not well known, the reductive dissolution of As-rich Fe oxyhydroxides has so far been a favorite hypothesis. Decoupling between arsenic and iron redox transformations has been experimentally demonstrated, but not quantitatively interpreted. Here, we report on incubation batch experiments run with As(V) sorbed on, or co-precipitated with, 2-line ferrihydrite. The biotic and abiotic processes of As release were investigated by using wet chemistry, X-ray diffraction, X-ray absorption and genomic techniques. The incubation experiments were carried out with a phosphate-rich growth medium and a community of Fe(III)-reducing bacteria under strict anoxic conditions for two months. During the first month, the release of Fe(II) in the aqueous phase amounted to only 3% to 10% of the total initial solid Fe concentration, whilst the total aqueous As remained almost constant after an initial exchange with phosphate ions. During the second month, the aqueous Fe(II) concentration remained constant, or even decreased, whereas the total quantity of As released to the solution accounted for 14% to 45% of the total initial solid As concentration. At the end of the incubation, the aqueous-phase arsenic was present predominately as As(III) whilst X-ray absorption spectroscopy indicated that more than 70% of the solid-phase arsenic was present as As(V). X-ray diffraction revealed vivianite Fe(II)3(PO4)2.8H2O in some of the experiments. A biogeochemical model was then developed to simulate these aqueous- and solid-phase results. The two main conclusions drawn from the model are that (1) As(V) is not reduced during the first incubation month with high Eh values, but rather re-adsorbed onto the ferrihydrite surface, and this state remains until arsenic reduction is energetically more favorable than iron reduction, and (2) the release of As during the second month is due to its reduction to the more weakly adsorbed As(III) which cannot compete against carbonate ions for sorption onto ferrihydrite. The model was also successfully applied to recent experimental results on the release of arsenic from Bengal delta sediments.
SAT, a flexible and optimized Web application for SSR marker development
Authors: Dereeper Alexis , Argout Xavier , Billot Claire , Rami Jean-François , Ruiz Manuel
Published: November 2007

Background

Simple Sequence Repeats (SSRs), or microsatellites, are among the most powerful genetic markers known. A common method for the development of SSR markers is the construction of genomic DNA libraries enriched for SSR sequences, followed by DNA sequencing. However, designing optimal SSR markers from bulk sequence data is a laborious and time-consuming process.

Results

SAT (SSR Analysis Tool) is a user-friendly Web application developed to minimize tedious manual operations and reduce errors. This tool facilitates the integration, analysis and display of sequence data from SSR-enriched libraries.

SAT is designed to successively perform base calling and quality evaluation of chromatograms, eliminate cloning vector, adaptors and low quality sequences, detect chimera or partially digested sequences, search for SSR motifs, cluster and assemble the redundant sequences, and design SSR primer pairs. An additional virtual PCR step establishes primer specificity. Users may modify the different parameters of each step of the SAT analysis.

Although certain steps are compulsory, such as SSR motifs search and sequence assembly, users do not have to run the entire pipeline, and they can choose selectively which steps to perform. A database allows users to store and query results, and to redo individual steps of the workflow.

Conclusion

The SAT Web application is available at http://sat.cirad.fr/sat, and a standalone command-line version is also freely downloadable. Users must send an email to the SAT administrator tropgene@cirad.fr to request a login and password.
Adiponectin and AMP kinase activator stimulate proliferation, differentiation, and mineralization of osteoblastic MC3T3-E1 cells
Authors: Kanazawa Ippei , Yamaguchi Toru , Yano Shozo , Yamauchi Mika , Yamamoto Masahiro , Sugimoto Toshitsugu
Published: November 2007

Background

Adiponectin is a key mediator of the metabolic syndrome that is caused by visceral fat accumulation. Adiponectin and its receptors are known to be expressed in osteoblasts, but their actions with regard to bone metabolism are still unclear. In this study, we investigated the effects of adiponectin on the proliferation, differentiation, and mineralization of osteoblastic MC3T3-E1 cells.

Results

Adiponectin receptor type 1 (AdipoR1) mRNA was detected in the cells by RT-PCR. The adenosine monophosphate-activated protein kinase (AMP kinase) was phosphorylated by both adiponectin and a pharmacological AMP kinase activator, 5-amino-imidazole-4-carboxamide-riboside (AICAR), in the cells. AdipoR1 small interfering RNA (siRNA) transfection potently knocked down the receptor mRNA, and the effect of this knockdown persisted for as long as 10 days after the transfection. The transfected cells showed decreased expressions of type I collagen and osteocalcin mRNA, as determined by real-time PCR, and reduced ALP activity and mineralization, as determined by von Kossa and Alizarin red stainings. In contrast, AMP kinase activation by AICAR (0.01–0.5 mM) in wild-type MC3T3-E1 cells augmented their proliferation, differentiation, and mineralization. BrdU assay showed that the addition of adiponectin (0.01–1.0 μg/ml) also promoted their proliferation. Osterix, but not Runx-2, appeared to be involved in these processes because AdipoR1 siRNA transfection and AICAR treatments suppressed and enhanced osterix mRNA expression, respectively.

Conclusion

Taken together, this study suggests that adiponectin stimulates the proliferation, differentiation, and mineralization of osteoblasts via the AdipoR1 and AMP kinase signaling pathways in autocrine and/or paracrine fashions.
TFCONES: A database of vertebrate transcription factor-encoding genes and their associated conserved noncoding elements
Authors: Lee Alison P , Yang Yuchen , Brenner Sydney , Venkatesh Byrappa
Published: November 2007

Background

Transcription factors (TFs) regulate gene transcription and play pivotal roles in various biological processes such as development, cell cycle progression, cell differentiation and tumor suppression. Identifyingcis-regulatory elements associated with TF-encoding genes is a crucial step in understanding gene regulatory networks. To this end, we have used a comparative genomics approach to identify putativecis-regulatory elements associated with TF-encoding genes in vertebrates.

Description

We have created a database named TFCONES (TranscriptionFactor Genes & AssociatedCOnservedNoncodingElementS) (http://tfcones.fugu-sg.org) which contains all human, mouse and fugu TF-encoding genes and conserved noncoding elements (CNEs) associated with them. The CNEs were identified by gene-by-gene alignments of orthologous TF-encoding gene loci using MLAGAN. We also predicted putative transcription factor binding sites within the CNEs. A significant proportion of human-fugu CNEs contain experimentally defined binding sites for transcriptional activators and repressors, indicating that a majority of the CNEs may function as transcriptional regulatory elements. The TF-encoding genes that are involved in nervous system development are generally enriched for human-fugu CNEs. Users can retrieve TF-encoding genes and their associated CNEs by conducting a keyword search or by selecting a family of DNA-binding proteins.

Conclusion

The conserved noncoding elements identified in TFCONES represent a catalog of highly prioritized putativecis-regulatory elements of TF-encoding genes and are candidates for functional assay.
Comparison of Genomes of Three Xanthomonas oryzae Bacteriophages
Authors: Lee Chia-Ni , Hu Rouh-Mei , Chow Teh-Yuan , Lin Juey-Wen , Chen Hui-Yi , Tseng Yi-Hsiung , Weng Shu-Fen
Published: November 2007

Background

Xp10 and OP1 are phages of Xanthomonas oryzae pv. oryzae (Xoo), the causative agent of bacterial leaf blight in rice plants, which were isolated in 1967 in Taiwan and in 1954 in Japan, respectively. We recently isolated the Xoo phage Xop411.

Results

The linear Xop411 genome (44,520 bp, 58 ORFs) sequenced here is 147 bp longer than that of Xp10 (60 ORFs) and 735 bp longer than that of OP1 (59 ORFs). The G+C contents of OP1 (51%) and Xop411 and Xp10 (52% each) are less than that of the host (65%). The 9-bp 3'-overhangs (5'-GGACAGTCT-3') in Xop411 and Xp10 are absent from OP1. More of the deduced Xop411 proteins share higher degrees of identity with Xp10 than with OP1 proteins, while the right end of the genomes of Xp10 and OP1, containing all predicted promoters, share stronger homology. Xop411, Xp10, and OP1 contain 8, 7, and 6 freestanding HNH endonuclease genes, respectively. These genes can be classified into five groups depending on their possession of the HNH domain (HNN or HNH type) and/or AP2 domain in intact or truncated forms. While the HNN-AP2 type endonuclease genes dispersed in the genome, the HNH type endonuclease genes, each with a unique copy, were located within the same genome context. Mass spectrometry and N-terminal sequencing showed nine Xop411 coat proteins, among which three were identified, six were assigned as coat proteins (4) and conserved phage proteins (2) in Xp10. The major coat protein, in which only the N-terminal methionine is removed, appears to exist in oligomeric forms containing 2 to 6 subunits. The three phages exhibit different patterns of domain duplication in the N-terminus of the tail fiber, which are involved in determination of the host range. Many short repeated sequences are present in and around the duplicated domains.

Conclusion

Geographical separation may have confined lateral gene transfer among the Xoo phages. The HNN-AP2 type endonucleases were more likely to transfer their genes randomly in the genome and may degenerate after successful transmission. Some repeated sequences may be involved in duplication/loss of the domains in the tail fiber genes.
Evolutionary conservation of plant gibberellin signalling pathway components
Authors: Vandenbussche Filip , Fierro Ana C , Wiedemann Gertrud , Reski Ralf , Van Der Straeten Dominique
Published: November 2007

Background:

Gibberellins (GA) are plant hormones that can regulate germination, elongation growth, and sex determination. They ubiquitously occur in seed plants. The discovery of gibberellin receptors, together with advances in understanding the function of key components of GA signalling in Arabidopsis and rice, reveal a fairly short GA signal transduction route. The pathway essentially consists of GID1 gibberellin receptors that interact with F-box proteins, which in turn regulate degradation of downstream DELLA proteins, suppressors of GA-controlled responses.

Results:

Arabidopsis sequences of the gibberellin signalling compounds were used to screen databases from a variety of plants, including protists, for homologues, providing indications for the degree of conservation of the pathway. The pathway as such appears completely absent in protists, the moss Physcomitrella patens shares only a limited homology with the Arabidopsis proteins, thus lacking essential characteristics of the classical GA signalling pathway, while the lycophyte Selaginella moellendorffii contains a possible ortholog for each component. The occurrence of classical GA responses can as yet not be linked with the presence of homologues of the signalling pathway. Alignments and display in neighbour joining trees of the GA signalling components confirm the close relationship of gymnosperms, monocotyledonous and dicotyledonous plants, as suggested from previous studies.

Conclusion:

Homologues of the GA-signalling pathway were mainly found in vascular plants. The GA signalling system may have its evolutionary molecular onset in Physcomitrella patens, where GAs at higher concentrations affect gravitropism and elongation growth.
Application of phage display to high throughput antibody generation and characterization
Authors: Schofield Darren J , Pope Anthony R , Clementel Veronica , Buckell Jenny , Chapple Susan DJ , Clarke Kay F , Conquer Jennie S , Crofts Anna M , Crowther Sandra RE , Dyson Michael R , Flack Gillian , Griffin Gareth J , Hooks Yvette , Howat William J , Kolb-Kokocinski Anja , Kunze Susan , Martin Cecile D , Maslen Gareth L , Mitchell Joanne N , O'Sullivan Maureen , Perera Rajika L , Roake Wendy , Shadbolt S Paul , Vincent Karen J , Warford Anthony , Wilson Wendy E , Xie Jane , Young Joyce L , McCafferty John
Published: November 2007

We have created a high quality phage display library containing over 1010 human antibodies and describe its use in the generation of antibodies on an unprecedented scale. We have selected, screened and sequenced over 38,000 recombinant antibodies to 292 antigens, yielding over 7,200 unique clones. 4,400 antibodies were characterized by specificity testing and detailed sequence analysis and the data/clones are available online. Sensitive detection was demonstrated in a bead based flow cytometry assay. Furthermore, positive staining by immunohistochemistry on tissue microarrays was found for 37% (143/381) of antibodies. Thus, we have demonstrated the potential of and illuminated the issues associated with genome-wide monoclonal antibody generation.
Symptom Prevalence, Intensity, and Distress in Patients With Inoperable Lung Cancer in Relation to Time of Death
Authors: Tishelman Carol , Petersson Lena-Marie , Degner Lesley F. , Sprangers Mirjam A.G.
Published: November 2007

Purpose

To examine symptom prevalence, intensity, and association with distress in patients with inoperable lung cancer (LC), using time to death as point of reference.

Patients and Methods

A consecutive sample of 400 patients completed the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire C30 plus a 13-item LC-specific scale and the Thurstone Scale of Symptom Distress–Lung Cancer at six time points during the first year after diagnosis. Patients were divided into subgroups, using data from the time point closest to death (< 1; 1 to 2; > 2 to 3; > 3 to 6; > 6 to 12; and > 12 months before death) for analysis.

Results

More than 50% of patients in all subgroups reported problems related to physical, role, and emotional functioning; fatigue; dyspnea; and cough. In general, functional levels were lower and symptoms higher in subgroups closer to death. Notably, clinically relevant differences were also found in role and social functioning and appetite loss between the two groups furthest from death. A consistent pattern was found among the six subgroups, with breathing, pain, and fatigue rated as the symptoms most associated with distress.

Conclusion

High prevalence of symptoms was found in all subgroups, with higher intensity in subgroups closer to death, indicating a need for prophylactic and proactive symptom management. Less concordance was found among symptom prevalence, intensity, and association with distress in subgroups further from death. Future studies should investigate longitudinal associations between symptoms with low intensity and high distress, and examine their clinical implications.
p53 Gene and Protein Status: The Role of p53 Alterations in Predicting Outcome in Patients With Bladder Cancer
Authors: George Ben , Datar Ram H. , Wu Lin , Cai Jie , Patten Nancy , Beil Stephen J. , Groshen Susan , Stein John , Skinner Donald , Jones Peter A. , Cote Richard J.
Published: November 2007

Purpose

The p53 gene status (mutation) and protein alterations (nuclear accumulation detectable by immunohistochemistry; p53 protein status) are associated with bladder cancer progression. Substantial discordance is documented between the p53 protein and gene status, yet no studies have examined the relationship between the gene-protein status and clinical outcome. This study evaluated the clinical relationship of the p53 gene and protein statuses.

Materials and Methods

The complete coding region of the p53 gene was queried using DNA from paraffin-embedded tissues and employing a p53 gene–sequencing chip. We compared p53 gene status, mutation site, and protein status with time to recurrence.

Results

The p53 gene and protein statuses show significant concordance, yet 35% of cases showed discordance. Exon 5 mutations demonstrated a wild-type protein status in 18 of 22 samples. Both the p53 gene and protein statuses were significantly associated with stage and clinical outcome. Specific mutation sites were associated with clinical outcome; tumors with exon 5 mutations showed the same outcome as those with the wild-type gene. Combining the p53 gene and protein statuses stratifies patients into three distinct groups, based on recurrence-free intervals: patients showing the best outcome (wild-type gene and unaltered protein), an intermediate outcome (either a mutated gene or an altered protein) and the worst outcome (a mutated gene and an altered protein).

Conclusion

We show that evaluation of both the p53 gene and protein statuses provides information in assessing the clinical recurrence risk in bladder cancer and that the specific mutation site may be important in assessing recurrence risk. These findings may substantially impact the assessment of p53 alterations and the management of bladder cancer.
Is There a Role for Pelvic Irradiation in Localized Prostate Adenocarcinoma? Preliminary Results of GETUG-01
Authors: Pommier Pascal , Chabaud Sylvie , Lagrange Jean Leon , Richaud Pierre , Lesaunier François , Le Prise Elisabeth , Wagner Jean Philippe , Hay Meng Huor , Beckendorf Veronique , Suchaud Jean Philippe , du Chatelard Pierre Marie Pabot , Bernier Valerie , Voirin Nicolas , Perol David , Carrie Christian
Published: November 2007

Purpose

To assess the benefit and toxicity and quality-of-life (QOL) outcomes of pelvic nodes irradiation in nonmetastatic prostate carcinoma patients.

Patients and Methods

Between December 1998 and June 2004, 444 patients with T1b-T3, N0 pNx, M0 prostate carcinoma were randomly assigned to either pelvic and prostate radiotherapy or prostate radiotherapy only. Patients were stratified according to the prognostic factor of lymph node involvement (LNI). Short-term 6-month neoadjuvant and concomitant hormonal therapy was allowed only for patients in the high-risk group. The pelvic dose was 46 Gy. The total dose recommended to the prostate was changed during the course of the study from 66 Gy to 70 Gy. Criteria for progression-free survival (PFS) included biologic prostate-specific antigen recurrences or a local or metastatic evolution. Acute and late toxicities were recorded according to the Radiation Therapy Oncology Group and Late Effects in Normal Tissues Subjective, Objective, Management, and Analytic scales, respectively. The QOL outcome was recorded with the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire C30, the International Prostatic Symptom Score, and the Sexual Function Index scales.

Results

With a 42.1-month median follow-up time, the 5-year PFS and overall survival were similar in the two treatment arms for the whole series and for each stratified group. On multivariate analysis, low LNI risk and hormonal therapy were statistically associated with increased PFS. However, subgroup analyses based on these factors did not show any benefit for pelvic irradiation. There were no significant differences in acute and late digestive toxicities and in QOL outcomes.

Conclusion

Pelvic node irradiation was well tolerated but did not improve PFS.
Chemotherapy Compared With Biochemotherapy for the Treatment of Metastatic Melanoma: A Meta-Analysis of 18 Trials Involving 2,621 Patients
Authors: Ives Natalie J. , Stowe Rebecca L. , Lorigan Paul , Wheatley Keith
Published: November 2007

Purpose

To assess the effect of adding interferon-α (IFN) ± interleukin-2 (IL-2) to chemotherapy in patients with metastatic melanoma.

Methods

A published data meta-analysis of trials of biochemotherapy versus chemotherapy in patients with metastatic melanoma was undertaken. End points evaluated were rates of partial response (PR), complete response (CR) and overall (partial + complete) response (OR); response duration; progression-free survival; overall survival (OS); and toxicity. The only subgroup analysis performed was by type of immunotherapy, with trials divided according to whether IFN only or IFN and IL-2 were administered in the biochemotherapy arm.

Results

Eighteen randomized trials were identified: 11 trials of chemotherapy ± IFN and seven trials of chemotherapy ± IFN and IL-2. More than 2,600 patients were entered onto the trials, with 555 responses and 2,039 deaths. There was a clear benefit for biochemotherapy for PR (odds ratio = 0.66; 95% CI, 0.53 to 0.82; P = .0001), CR (odds ratio = 0.50; 95% CI, 0.35 to 0.73; P = .0003) and OR (odds ratio = 0.59; 95% CI, 0.49 to 0.72; P < .00001). For OR, these benefits were significant for both the IFN (odds ratio = 0.60; 95% CI, 0.46 to 0.79; P = .0002) and IFN + IL-2 (odds ratio = 0.58; 95% CI, 0.44 to 0.77; P = .0001) subgroups. In contrast, there was no benefit overall in OS (odds ratio = 0.99; 95% CI, 0.91 to 1.08; P = .9), but there was evidence of heterogeneity of treatment effect between the individual trials (P = .006).

Conclusion

This meta-analysis provides a comprehensive summary of all the data currently available, and shows that although biochemotherapy clearly improves response rates, this does not appear to translate into a survival benefit.
Positron Emission Tomography for Staging of Pediatric Sarcoma Patients: Results of a Prospective Multicenter Trial
Authors: Völker Thomas , Denecke Timm , Steffen Ingo , Misch Daniel , Schönberger Stefan , Plotkin Michail , Ruf Juri , Furth Christian , Stöver Brigitte , Hautzel Hubertus , Henze Günter , Amthauer Holger
Published: November 2007

Purpose

The objective of this study was to evaluate the impact of positron emission tomography (PET) using fluorine-18–fluorodeoxyglucose (FDG) for initial staging and therapy planning in pediatric sarcoma patients.

Patients and Methods

In this prospective multicenter study, 46 pediatric patients (females, n = 22; males, n = 24; age range, 1 to 18 years) with histologically proven sarcoma (Ewing sarcoma family tumors, n = 23; osteosarcoma, n = 11; rhabdomyosarcoma, n = 12) were examined with conventional imaging modalities (CIMs), including ultrasound, computed tomography (CT), magnetic resonance imaging, and bone scintigraphy according to the standardized algorithms of the international therapy optimization trials, and whole-body FDG-PET. A lesion- and patient-based analysis of PET alone and CIMs alone and a side-by-side (SBS) analysis of FDG-PET and CIMs were performed. The standard of reference consisted of all imaging material, follow-up data (mean follow-up time, 24 ± 12 months), and histopathology and was determined by an interdisciplinary tumor board.

Results

FDG-PET and CIMs were equally effective in the detection of primary tumors (accuracy, 100%). PET was superior to CIMs concerning the correct detection of lymph node involvement (sensitivity, 95% v 25%, respectively) and bone manifestations (sensitivity, 90% v 57%, respectively), whereas CT was more reliable than FDG-PET in depicting lung metastases (sensitivity, 100% v 25%, respectively). The patient-based analysis revealed the best results for SBS, with 91% correct therapy decisions. This was significantly superior to CIMs (59%; P < .001).

Conclusion

In staging pediatric sarcoma, subsidiary FDG-PET scanning depicts important additional information and has a relevant impact on therapy planning when analyzed side-by-side with CIMs.
Prospective Study of a Pirarubicin, Intermediate-Dose Cytarabine, and Etoposide Regimen in Children With Down Syndrome and Acute Myeloid Leukemia: The Japanese Childhood AML Cooperative Study Group
Authors: Kudo Kazuko , Kojima Seiji , Tabuchi Ken , Yabe Hiromasa , Tawa Akio , Imaizumi Masue , Hanada Ryoji , Hamamoto Kazuko , Kobayashi Ryoji , Morimoto Akira , Nakayama Hideki , Tsuchida Masahiro , Horibe Keizo , Kigasawa Hisato , Tsukimoto Ichiro
Published: November 2007

Purpose

To evaluate a less intensive chemotherapeutic regimen specifically designed for patients with Down syndrome (DS) and acute myeloid leukemia (AML), and to determine the prognostic factors for event-free survival.

Patients and Methods

Seventy-two patients with AML-DS were treated with remission induction chemotherapy consisting of pirarubicin (25 mg/m2/d for 2 days), cytarabine (100 mg/m2/d for 7 days), and etoposide (150 mg/m2/d for 3 days). Patients received four courses of intensification therapy of the same regimen. Prophylaxis for CNS leukemia was not included.

Results

All but two patients were younger than 4 years, and 67 of the 72 patients (93%) were diagnosed as acute megakaryoblastic leukemia (AMKL). Seventy of the 72 patients (97.2%) achieved a complete remission (CR), and the estimated 4-year event-free survival (EFS) rate was 83% ± 9%. Nine patients relapsed, and one died as a result of pneumonia during CR. Multivariate analysis revealed that the presence of monosomy 7 was a greater risk factor of adverse outcome (odds ratio = 5.67; P = .027).

Conclusion

A less intensive chemotherapeutic regimen produces excellent outcomes in standard-risk AML-DS patient. Risk-oriented therapy should be considered for future trials in AML-DS.
Randomized Double-Blind Trial of Prophylactic Oral Minocycline and Topical Tazarotene for Cetuximab-Associated Acne-Like Eruption
Authors: Scope Alon , Agero Anna Liza C. , Dusza Stephen W. , Myskowski Patricia L. , Lieb Jocelyn A. , Saltz Leonard , Kemeny Nancy E. , Halpern Allan C.
Published: November 2007

Purpose

To evaluate the ability of either oral minocycline, topical tazarotene or both, to reduce or prevent cetuximab-related acneiform rash when administered starting on day 1 of cetuximab therapy.

Patients and Methods

Metastatic colorectal cancer patients preparing to initiate cetuximab were randomly assigned to receive daily oral minocycline or placebo, and to receive topical tazarotene application to either left or right side of the face. Both therapies were administered for 8 weeks.

Results

Forty-eight eligible patients were randomly assigned to minocycline (n = 24) or placebo (n = 24). Total facial lesion counts were significantly lower in patients receiving minocycline at weeks 1 through 4. At week 4, a lower proportion of patients in the minocycline arm reported moderate to severe itch than in the placebo arm (20% v 50%, P = .05). Facial photographs, obtained at week 4, were reviewed for rash global severity. Patients in the minocycline arm trended toward lower frequency of moderate to severe rash than patients receiving placebo (20% v 42%, P = .13). The differences in total facial lesion counts and subjectively assessed itch were diminished by week 8. Cetuximab treatment was interrupted because of grade 3 skin rash in four patients in the placebo arm, and none in the minocycline arm. There was no observed clinical benefit to tazarotene application. Tazarotene treatment was associated with significant irritation, causing its discontinuation in one third of patients.

Conclusion

Prophylaxis with oral minocycline may be useful in decreasing the severity of the acneiform rash during the first month of cetuximab treatment. Topical tazarotene is not recommended for management of cetuximab-related rash.
A novel promoter-tethering element regulates enhancer-driven gene expression at the bithorax complex in theDrosophilaembryo
Authors: Akbari Omar S. , Bae Esther , Johnsen Holly , Villaluz Alfred , Wong Debbie , Drewell Robert A.
Published: November 2007

A key question in our understanding of the cis-regulation of gene expression during embryonic development has been the molecular mechanism that directs enhancers to specific promoters within a gene complex. Promoter competition and insulators are thought to play a role in regulating these interactions. In the bithorax complex of Drosophila, the IAB5 enhancer is located 55 kb 3′ of the Abdominal-B(Abd-B) promoter and 48 kb 5′ of the abdominal-A(abd-A) promoter. Although roughly equidistant from the two promoters, IAB5 specifically interacts only with the Abdominal-Bpromoter, even though the enhancer and promoter are separated by at least two insulators. Here we demonstrate that a 255 bp element, located 40 bp 5′of the Abd-B transcriptional start site, has a novel cis-regulatory activity as it is able to tether IAB5 to the Abd-B promoter in transgenic embryos. The tethering element is sufficient to direct IAB5 to an ectopic promoter in competition assays. Deletion of the promoter-tethering element results in the redirection of enhancer-driven gene expression on transgenes. Taken together, these results provide evidence that specific long-range enhancer-promoter interactions in the bithorax complex are regulated by a tethering element 5′ of the Abd-B promoter. We discuss a bioinformatic analysis of the tethering element across different Drosophila species and a possible molecular mechanism by which this element functions. We also examine existing evidence that this novel class of cis-regulatory elements might regulate enhancer-promoter specificity at other gene complexes.