bluuebunny/crossref_metadata_2025 huggingface dataset:
Cell-Based Therapy for Myocardial Ischemia and Infarction: Pathophysiological Mechanisms
Authors: Laflamme Michael A. , Zbinden Stephan , Epstein Stephen E. , Murry Charles E.
Published: January 2007

Cell-based cardiac repair has emerged as an attractive approach to preventing or reversing heart failure resulting from myocyte dysfunction—e.g., due to infarction—and to enhancing the development of collaterals in patients with symptoms of myocardial ischemia. These two problems involve both overlapping and differing mechanisms, and these differences must be considered in cell-based therapies. In terms of myocardial dysfunction due to infarction, only committed cardiomyocytes have been shown to form new myocardium that is electrically coupled with the host heart. Despite this, multiple cell populations appear to improve function of the infarcted heart, including many that are clearly nonmyogenic. In terms of myocardial ischemia, although cell-based strategies improve ischemia in animal models, clinical trials to date have not shown robustly beneficial results. We review the evidence for potential mechanisms underlying the benefits of cell transplantation in the heart and discuss the clinical contexts in which they may be relevant.
VEGF-A and the Induction of Pathological Angiogenesis
Authors: Nagy Janice A. , Dvorak Ann M. , Dvorak Harold F.
Published: January 2007

Tumors, wounds, and chronic inflammatory disorders generate a new vascular supply by a process known as pathological angiogenesis. Whereas formation of the normal blood vasculature requires the interaction of many different agonists and inhibitors, including vascular endothelial growth factor-A (VEGF-A) and other members of the vascular permeability factor/VEGF family, pathological angiogenesis is a cruder, simpler process that can be replicated by a single VEGF-A isoform, VEGF-A164/5. VEGF-A164/5induces the formation of several distinctly different types of new blood vessels that differ from normal blood vessels with respect to organization, structure, and function. Elucidating the properties of these new vessels has led to a better understanding of angiogenesis and will hopefully lead to new approaches to antiangiogenic therapy.
Genetic Susceptibility to Essential Hypertension
Authors: Lalouel Jean-Marc , Rohrwasser Andreas
Published: January 2007

Although progress in the genetics of essential hypertension may seem disappointing, it has considerable potential in defining research directions that will ultimately translate into clinical practice. The hypothesis that genetic variation at the angiotensinogen locus impacts on individual susceptibility to develop essential hypertension has motivated a substantial body of research by us and many others. We examine how analyses of the mechanisms by which variation in angiotensinogen expression may contribute to disease susceptibility and may have arisen in human populations have progressed in recent years. Although the objective of personalized medicine is still in the future, a genetic hypothesis based on human variation can uniquely empower functional genomics approaches to reach such an ultimate goal.
Population Pharmacokinetics of Humanized Monoclonal Antibody HuCC49ΔCH2 and Murine Antibody CC49 in Colorectal Cancer Patients
Authors: Fang Lanyan , Holford Nicholas H. G. , Hinkle George , Cao Xianhua , Xiao Jim J. , Bloomston Mark , Gibbs Seth , Al Saif Osama Habib , Dalton James T. , Chan Kenneth K. , Schlom Jeffery , Martin Edward W. , Sun Duxin
Published: January 2007

To predict the optimal time for surgery after antibody administration, the population pharmacokinetics of 125I‐HuCC49ΔCH2 and 125I‐CC49 were characterized in 55 patients with colorectal cancers. A 2‐compartment linear model was used to fit the pharmacokinetic data. Model stability and performance were assessed using a visual predictive check procedure. Different clinical trial designs were evaluated by simulation in combination with Bayesian estimation method to predict the optimal time for surgery. The results showed that HuCC49ΔCH2 had 65% faster clearance from blood circulation and 24% shorter mean residence time than CC49. Population pharmacokinetic analysis identified body weight as the only covariate to explain between‐subject variability in clearance, intercompartmental flow rate, and volume of distribution. Model predictions indicated a wide interval for the optimal time of surgery, suggesting that it would be beneficial to individualize the time of surgery for each patient by measurement of antibody disposition. Clinical trial designs with at least 3 measurements of antibody disposition were found to be better than an empirical direct observation method for the optimal prediction of surgery time.
A Multisite Study of Community Treatment Programs for Mentally Ill Offenders With Major Mental Disorders
Authors: Hodgins Sheilagh , Tengström Anders , Eriksson Asa , Österman Reidar , Kronstrand Robert , Eaves Derek , Hart Stephen , Webster Christopher , Ross Deborah , Levin Alexander , Levander Sten , Tuninger Eva , Müller-Isberner Rüdiger , Freese Roland , Tiihonen Jari , Kotilainen Irma , Repo-Tiihonen Eila , Väänänen Kirsi , Eronen Markku , Vokkolainen Aila , Vartiainen Heikki
Published: January 2007

This article presents reasons for undertaking “The Comparative Study of the Prevention of Crime and Violence by Mentally Ill Persons” and reasons for decisions regarding the study design and choice of measures. A brief portrait of the forensic patients that have been recruited is also presented. Community treatment programs could offer long-term cost-effective care for offenders with major mental disorders (MMDs). The study aims to identify the necessary ingredients of an effective program. Sites are selected in four countries where identification of most, if not all, persons with MMD who commit crimes within the catchment area was possible. Within each site, two samples of patients with MMD are recruited, one from a forensic hospital and one from a general psychiatric hospital. Assessments are completed prior to discharge. Participants are followed during a 5-year period. Comparisons of the forensic patients recruited in the four sites indicate many more similarities than differences.
Sequestering Gang Members, Burning Witches, and Subverting Due Process
Authors: Toch Hans
Published: January 2007

There are striking parallels between the procedures relied on by medieval inquisitors in persecuting witches and those used by American prison administrators in “classification” proceedings through which gang members are indefinitely sequestered based on evidence of gang affiliation. In both cases, due process is nominal and minimal, there is considerable reliance on information obtained from confidential informants, personal stigmata are summated and submitted as incriminating evidence, and defendants are encouraged to confess and debrief. In both cases, the advertised goal of the process involves concern for safety and survival of the system. In the case of prisons, this goal gains credence from the fact that most efforts to monitor and control gang behavior have had limited success. The experience of failure has been understandably frustrating for prison officials, and recourse to the punitive segregation of gang members (under the guise of preempting gang violence) represents a measure of this frustration.
The Art and Science of Surgery: Innovation and Concepts of Medical Practice in Operative Fracture Care, 1960s–1970s
Authors: Schlich Thomas
Published: January 2007

In this article, I am using the example of the introduction of osteosynthesis into surgical routine practice to analyze the use of the notions of art and science in medical innovation. The examination of the renegotiations of power and responsibility associated with the introduction of this new technique shows that proponents and critics actively linked their arguments to more fundamental epistemological and social issues. The proponents claimed to manage the uncertainties of innovation through making surgery more scientific, drawing on the ideals of control, rationality, objectivity, and predictability. The critics mobilized another discursive pattern. They considered surgery an art and emphasized the individuality, contingency, and situatedness of medical practice. I investigate the discursive function of these argumentative patterns and how they played out in the concrete example of this surgical technique.
Evaluating the Communication Satisfaction Questionnaire as a Communication Audit Tool
Authors: Zwijze-Koning Karen , de Jong Menno
Published: January 2007

Despite the number of publications about auditing organizational communication, scholars have paid little attention to the reliability and validity of individual audit techniques. This study examines the merits and restrictions of the Communication Satisfaction Questionnaire (CSQ) by comparing CSQ results with results gathered with the critical incident technique. The authors used both instruments to assess the quality of internal communication within three organizations. They found that the two techniques converge and that the CSQ appears to have criterion-related validity. However, the CSQ fails to explicitly address issues of decision making, top-down and bottom-up communication, responsibilities, and the extent to which organizations keep rules and agreements. The authors conclude that the CSQ is an appropriate instrument for gaining overall insights into the way employees evaluate aspects of organizational communication but that the method is less suitable for diagnosing specific communication problems and formulating recommendations.
The Impact of Gender and Organizational Status on Workplace Anger Expression
Authors: Domagalski Theresa A. , Steelman Lisa A.
Published: January 2007

The social rules for communicating anger in the workplace are multifaceted, and standards vary for different groups. Previous research addresses either gender differences in anger expression or organizational status differences, but not the combined impact of gender and status. The authors close this gap by investigating both the independent and joint influence of gender and relative organizational status on workplace anger expression. Their findings show that emotional restraint is the most frequent method of handling anger across all groups. Lower status males, however, directly express their anger around higher status members significantly more frequently than do lower status females. The authors conclude with observations regarding the relative strength of organizational norms as compared to gender-based norms.
Children's socialization into cleaning practices: a cross-cultural perspective
Authors: Fasulo Alessandra , Loyd Heather , Padiglione Vincenzo
Published: January 2007

Focusing on everyday hygiene and household cleaning tasks, this study examines the socialization practices and parenting strategies that foster familial and cultural values such as autonomy, interdependence and responsibility. Through the micro-analysis of videotaped family interaction in Los Angeles and Rome, this article looks at actual practices and activity trajectories to reveal the ways in which families organize themselves, attach values to different aspects of activities, and build diverse perspectives on authoritativeness. The comparative analysis points to differences across cultures, families and activities in the style and amount of parental control over cleaning tasks, and the number of options given to children in the process and sequence of tasks. Examinations of diverse parenting and conversational strategies reveal how particular practices may lead to the construction or limitation of children's agency.
Lessons from sports: children's socialization to values through family interaction during sports activities
Authors: Kremer-Sadlik Tamar , Kim Jeemin Lydia
Published: January 2007

In the United States, children are encouraged to enroll in sports activities. Studies show that these activities are positively associated with reduced delinquent behavior and increased academic and social performance. Research using parents' reports in interviews and surveys shows that parents view extracurricular sports activities as an arena for socializing their children to important values and skills that go beyond the benefits of participation in athletic activities. Through analysis of parent–child interaction using video data of naturalistic family interaction during formal participation in organized sports (e.g. Little League), informal participation (e.g. backyard pick-up games), and passive participation in sports (e.g. watching televised athletic events), this article reveals that parents play an active role in this socialization process. This article underscores the important function that sports have in family daily life as a socializing tool for culturally cherished skills and values.
Integrated Active Fiber Composite Elements: Characterization for Acoustic Emission and Acousto-ultrasonics
Authors: Barbezat Michel , Brunner Andreas J. , Huber Christian , Flüeler Peter
Published: January 2007

Active fiber composites (AFC) made from piezoelectric fibers show promising potential, not only as actuators integrated into smart composites but also as sensors. Selected sensor properties of AFC elements are investigated with methods from acoustic emission sensor characterization and verification and from acousto-ultrasonic testing. Model experiments with AFC elements integrated in simple composite structures show that the various approaches for analysis of acousto-ultrasonic data yield indications of damage accumulation.
68 Cents per Song
Authors: Sandulli Francesco D. , Martin-Barbero Samuel
Published: January 2007

This article tries to find out how much and why the users of Peer-to-Peer (P2P) networks may be willing to pay for a digital song at online music stores, when they can also download songs for free via these networks. Based on a sample of more than 4000 Spanish P2P users, the empirical research reveals how a perceived greater value and a more intensive prosecution policy of copyright violations will boost their willingness to pay for online music.
War, Art and the Internet
Authors: Brandon Laura
Published: January 2007

The internet facilitates outrage, encourages debate, and ultimately accommodates balanced response. It allows for knowledge to be acquired and then shaped into shared meanings and understandings. Even if the digital record of the mainstream media is perhaps the more informed and balanced, the arguably greater significance of the internet - content aside - lies in its exemplification of the value of free communication. This argument is explored in the context of two 1996 paintings by contemporary Canadian painter Gertrude Kearns. The works were the subject of controversy when they went on display at the new Canadian War Museum, which opened on 5 May 2005. While Kearns’s works had previously been reproduced in a newspaper and a journal, they had not been exhibited in public before. The two compositions portray Master Corporal Clayton Matchee and Private Kyle Brown, the Canadian soldiers responsible for the 1993 murder of Shidane Arone, a Somali youth.
Staging restorative justice encounters against a criminal justice backdrop
Authors: Dignan James , Atkinson Anne , Atkinson Helen , Howes Marie , Johnstone Jennifer , Robinson Gwen , Shapland Joanna , Sorsby Angela
Published: January 2007

Drawing from an ongoing evaluation of three major restorative justice schemes in England and Wales, the article employs a dramaturgical perspective to examine a number of process issues that arise when restorative justice processes are deployed within a criminal justice context. They include the rôle and identity of restorative justice facilitators, the locations for restorative justice encounters and associated matters relating to the values of privacy, openness and accountability.
Chromosome painting in the manatee supports Afrotheria and Paenungulata
Authors: Kellogg Margaret E , Burkett Sandra , Dennis Thomas R , Stone Gary , Gray Brian A , McGuire Peter M , Zori Roberto T , Stanyon Roscoe
Published: January 2007

Background

Sirenia (manatees, dugongs and Stellar's sea cow) have no evolutionary relationship with other marine mammals, despite similarities in adaptations and body shape. Recent phylogenomic results place Sirenia in Afrotheria and with elephants and rock hyraxes in Paenungulata. Sirenia and Hyracoidea are the two afrotherian orders as yet unstudied by comparative molecular cytogenetics. Here we report on the chromosome painting of the Florida manatee.

Results

The human autosomal and X chromosome paints delimited a total of 44 homologous segments in the manatee genome. The synteny of nine of the 22 human autosomal chromosomes (4, 5, 6, 9, 11, 14, 17, 18 and 20) and the X chromosome were found intact in the manatee. The syntenies of other human chromosomes were disrupted in the manatee genome into two to five segments. The hybridization pattern revealed that 20 (15 unique) associations of human chromosome segments are found in the manatee genome: 1/15, 1/19, 2/3 (twice), 3/7 (twice), 3/13, 3/21, 5/21, 7/16, 8/22, 10/12 (twice), 11/20, 12/22 (three times), 14/15, 16/19 and 18/19.

Conclusion

There are five derived chromosome traits that strongly link elephants with manatees in Tethytheria and give implicit support to Paenungulata: the associations 2/3, 3/13, 8/22, 18/19 and the loss of the ancestral eutherian 4/8 association. It would be useful to test these conclusions with chromosome painting in hyraxes. The manatee chromosome painting data confirm that the associations 1/19 and 5/21 phylogenetically link afrotherian species and show that Afrotheria is a natural clade. The association 10/12/22 is also ubiquitous in Afrotheria (clade I), present in Laurasiatheria (clade IV), only partially present in Xenarthra (10/12, clade II) and absent in Euarchontoglires (clade III). If Afrotheria is basal to eutherians, this association could be part of the ancestral eutherian karyotype. If afrotherians are not at the root of the eutherian tree, then the 10/12/22 association could be one of a suite of derived associations linking afrotherian taxa.
Verruculogen associated with Aspergillus fumigatus hyphae and conidia modifies the electrophysiological properties of human nasal epithelial cells
Authors: Khoufache Khaled , Puel Olivier , Loiseau Nicolas , Delaforge Marcel , Rivollet Danièle , Coste André , Cordonnier Catherine , Escudier Estelle , Botterel Françoise , Bretagne Stéphane
Published: January 2007

Background

The role of Aspergillus fumigatus mycotoxins in the colonization of the respiratory tract by conidia has not been studied extensively, even though patients at risk from invasive aspergillosis frequently exhibit respiratory epithelium damage. In a previous study, we found that filtrates of A. fumigatus cultures can specifically alter the electrophysiological properties of human nasal epithelial cells (HNEC) compared to those of non pathogenic moulds.

Results

We fractionated the organic phase of filtrate from 3-day old A. fumigatus cultures using high-performance liquid chromatography. The different fractions were tested for their ability to modify the electrophysiological properties of HNEC in an in vitro primary culture model.

The fraction collected between 20 and 30 min mimicked the effects of the whole filtrate, i.e. decrease of transepithelial resistance and increase of potential differences, and contained secondary metabolites such as helvolic acid, fumagillin, and verruculogen. Only verruculogen (10-8 M) had effects similar to the whole filtrate. We verified that verruculogen was produced by a collection of 67 human, animal, plant and environmental A. fumigatus isolates. Using MS-MS analysis, we found that verruculogen was associated with both mycelium and conidia extracts.

Conclusion

Verruculogen is a secondary metabolite that modifies the electrophysiological properties of HNEC. The role of these modifications in the colonization and invasion of the respiratory epithelium by A. fumigatus on first contact with the epithelium remains to be determined.
National study of United States emergency department visits for acute pancreatitis, 1993–2003
Authors: Fagenholz Peter J , Fernández-del Castillo Carlos , Harris N Stuart , Pelletier Andrea J , Camargo Carlos A
Published: January 2007

Background

The epidemiology of acute pancreatitis in the United States is largely unknown, particularly episodes that lead to an emergency department (ED) visit. We sought to address this gap and describe ED practice patterns.

Methods

Data were collected from the National Hospital Ambulatory Medical Care Survey between 1993 and 2003. We examined demographic factors and ED management including medication administration, diagnostic imaging, and disposition.

Results

ED visits for acute pancreatitis increased over the study period from the 1994 low of 128,000 visits to a 2003 peak of 318,000 visits (p = 0.01). The corresponding ED visit rate per 10,000 U.S. population also increased from 4.9 visits (95%CI, 3.1–6.7) to 10.9 (95%CI, 7.6–14.3) (p = 0.01). The average age for patients making ED visits for acute pancreatitis during the study period was 49.7 years, 54% were male, and 27% were black. The ED visit rate was higher among blacks (14.7; 95%CI, 11.9–17.5) than whites (5.8; 95%CI, 5.0–6.6). At 42% of ED visits, patients did not receive analgesics. At 10% of ED visits patients underwent CT or MRI imaging, and at 13% of visits they underwent ultrasound testing. Two-thirds of ED visits resulted in hospitalization. Risk factors for hospitalization were older age (multivariate odds ratio for each increasing decade 1.5; 95%CI, 1.3–1.8) and white race (multivariate odds ratio 2.3; 95%CI, 1.2–4.6).

Conclusion

ED visits for acute pancreatitis are rising in the U.S., and ED visit rates are higher among blacks than whites. At many visits analgesics are not administered, and diagnostic imaging is rare. There was greater likelihood of admission among whites than blacks. The observed race disparities in ED visit and admission rates merit further study.
Morbidity and related factors among elderly people in South Korea: results from the Ansan Geriatric (AGE) cohort study
Authors: Woo Eun-kyung , Han Changsu , Jo Sangmee Ahn , Park Min Kyu , Kim Sungsoo , Kim Eunkyung , Park Moon Ho , Lee Juyoung , Jo Inho
Published: January 2007

Background

A thorough examination of the morbidity and comorbidity profiles among the elderly and an evaluation of the related factors are required to improve the delivery of health care to the elderly and to estimate the cost of that care. In South Korea where the aged population is rapidly increasing, however, to date only one study using a limited sample (84 subjects) has provided information on morbidity and related factors among the elderly. Using a large, stratified, random sample (2,767 subjects) from the population-based Ansan Geriatric study, the present study sought to assess the morbidity and comorbidity, and to determine the relationships of these variables with sociodemographic and health characteristics in elderly people in South Korea.

Methods

A total of 2,767 subjects (1,215 men and 1,552 women) aged 60–84 years were randomly selected from September 2002 to August 2003 in Ansan, South Korea. Data on sociodemographic and health characteristics, and clinical diagnosis were collected using questionnaires. When available, the medical records and medications taken by the subjects were also cross-checked.

Results

Of the total subjects, 78.0% reported diagnosed disease, 11.0% had been cured, and 46.8% had been diagnosed with more than two diseases. The mean number of morbidities per person among elderly Koreans was 1.62 ± 1.35 (mean ± standard deviation), and women had a greater number of diseases per person than did men. The most common morbidities were chronic diseases such as hypertension, arthritis, and diabetes mellitus. In women, osteoporosis and arthritis were the second and third most prevalent diseases, respectively. Morbidity was significantly associated with gender, employment, household income, alcohol intake, self-assessed health status, and worries about health.

Conclusion

These data will enhance understanding of the patterns of health problems among elderly Koreans and will contribute to the application of appropriate intervention strategies.
Effect of cyclooxygenase inhibition on cholesterol efflux proteins and atheromatous foam cell transformation in THP-1 human macrophages: a possible mechanism for increased cardiovascular risk
Authors: Chan Edwin SL , Zhang Hongwei , Fernandez Patricia , Edelman Sari D , Pillinger Michael H , Ragolia Louis , Palaia Thomas , Carsons Steven , Reiss Allison B
Published: January 2007

Both selective cyclooxygenase (COX)-2 inhibitors and non-steroidal anti-inflammatory drugs (NSAIDs) have been beneficial pharmacological agents for many patients suffering from arthritis pain and inflammation. However, selective COX-2 inhibitors and traditional NSAIDs are both associated with heightened risk of myocardial infarction. Possible pro-atherogenic mechanisms of these inhibitors have been suggested, including an imbalance in prostanoid production leaving the pro-aggregatory prostaglandins unopposed, but the precise mechanisms involved have not been elucidated. We explored the possibility that downregulation of proteins involved in reverse cholesterol transport away from atheromatous plaques contributes to increased atherogenesis associated with COX inhibition. The reverse cholesterol transport proteins cholesterol 27-hydroxylase and ATP-binding cassette transporter A1 (ABCA1) export cholesterol from macrophages. When mechanisms to process lipid load are inadequate, uncontrolled cholesterol deposition in macrophages transforms them into foam cells, a key element of atheromatous plaques. We showed that in cultured THP-1 human monocytes/macrophages, inhibition of COX-1, COX-2, or both reduced expression of 27-hydroxylase and ABCA1 message (real-time reverse transcription-polymerase chain reaction) and protein (immunoblot). The selective COX-2 inhibitor N-(2-cyclohexyloxy-4-nitrophenyl)methanesulfonamide (NS398) significantly reduced 27-hydroxylase and ABCA1 message (to 62.4% ± 2.2% and 71.1% ± 3.9% of control, respectively). Incubation with prostaglandin (PG) E2 or PGD2 reversed reductions in both of these cholesterol transport proteins induced by NS398. Cholesterol-loaded THP-1 macrophages showed significantly increased foam cell transformation in the presence of NS398 versus control (42.7% ± 6.6% versus 20.1% ± 3.4%, p = 0.04) as determined by oil red O staining. Pharmacological inhibition of COX in monocytes is involved in downregulation of two proteins that mediate cholesterol efflux: cholesterol 27-hydroxylase and ABCA1. Because these proteins are anti-atherogenic, their downregulation may contribute to increased incidence of cardiac events in patients treated with COX inhibitors. Reversal of inhibitory effects on 27-hydroxylase and ABCA1 expression by PGD2 and PGE2 suggests involvement of their respective signaling pathways. NS398-treated THP-1 macrophages show greater vulnerability to form foam cells. Increased cardiovascular risk with COX inhibition may be ascribed at least in part to altered cholesterol metabolism.
Impairment of organ-specific T cell negative selection by diabetes susceptibility genes: genomic analysis by mRNA profiling
Authors: Liston Adrian , Hardy Kristine , Pittelkow Yvonne , Wilson Susan R , Makaroff Lydia E , Fahrer Aude M , Goodnow Christopher C
Published: January 2007

Background

T cells in the thymus undergo opposing positive and negative selection processes so that the only T cells entering circulation are those bearing a T cell receptor (TCR) with a low affinity for self. The mechanism differentiating negative from positive selection is poorly understood, despite the fact that inherited defects in negative selection underlie organ-specific autoimmune disease in AIRE-deficient people and the non-obese diabetic (NOD) mouse strain

Results

Here we use homogeneous populations of T cells undergoing either positive or negative selection in vivo together with genome-wide transcription profiling on microarrays to identify the gene expression differences underlying negative selection to an Aire-dependent organ-specific antigen, including the upregulation of a genomic cluster in the cytogenetic band 2F. Analysis of defective negative selection in the autoimmune-prone NOD strain demonstrates a global impairment in the induction of the negative selection response gene set, but little difference in positive selection response genes. Combining expression differences with genetic linkage data, we identify differentially expressed candidate genes, including Bim, Bnip3, Smox, Pdrg1, Id1, Pdcd1, Ly6c, Pdia3, Trim30 and Trim12.

Conclusion

The data provide a molecular map of the negative selection response in vivo and, by analysis of deviations from this pathway in the autoimmune susceptible NOD strain, suggest that susceptibility arises from small expression differences in genes acting at multiple points in the pathway between the TCR and cell death.
Creating a honey bee consensus gene set
Authors: Elsik Christine G , Mackey Aaron J , Reese Justin T , Milshina Natalia V , Roos David S , Weinstock George M
Published: January 2007

Background

We wished to produce a single reference gene set for honey bee (Apis mellifera). Our motivation was twofold. First, we wished to obtain an improved set of gene models with increased coverage of known genes, while maintaining gene model quality. Second, we wished to provide a single official gene list that the research community could further utilize for consistent and comparable analyses and functional annotation.

Results

We created a consensus gene set for honey bee (Apis mellifera) using GLEAN, a new algorithm that uses latent class analysis to automatically combine disparate gene prediction evidence in the absence of known genes. The consensus gene models had increased representation of honey bee genes without sacrificing quality compared with any one of the input gene predictions. When compared with manually annotated gold standards, the consensus set of gene models was similar or superior in quality to each of the input sets.

Conclusion

Most eukaryotic genome projects produce multiple gene sets because of the variety of gene prediction programs. Each of the gene prediction programs has strengths and weaknesses, and so the multiplicity of gene sets offers users a more comprehensive collection of genes to use than is available from a single program. On the other hand, the availability of multiple gene sets is also a cause for uncertainty among users as regards which set they should use. GLEAN proved to be an effective method to combine gene lists into a single reference set.
Signaling through Gαi2 protein is required for recruitment of neutrophils for antibody-mediated elimination of larvalStrongyloides stercoralisin mice
Authors: Padigel Udaikumar M , Stein Louis , Redding Kevin , Lee James J , Nolan Thomas J , Schad Gerhard A , Birnbaumer Lutz , Abraham David
Published: January 2007

The heterotrimeric guanine nucleotide-binding protein Gαi2 is involved in regulation of immune responses against microbial and nonmicrobial stimuli. Gαi2−/− mice have a selectively impaired IgM response consistent with a disorder in B cell development yet have augmented T cell effector function associated with increased production of IFN-γ and IL-4. The goal of the present study was to determine if a deficiency in the Gαi2 protein in mice would affect the protective immune response against Strongyloides stercoralis, which is IL-4-, IL-5-, and IgM-dependent. Gαi2−/− and wild-type mice were immunized and challenged with S. stercoralis larvae and analyzed for protective immune responses against infection. Gαi2−/− mice failed to kill the larvae in the challenge infection as compared with wild-type mice despite developing an antigen-specific Th2 response characterized by increased IL-4, IL-5, IgM, and IgG. Transfer of serum collected from immunized Gαi2−/− mice to naïve wild-type mice conferred passive protective immunity against S. stercoralis infection thus confirming the development of a protective antibody response in Gαi2−/− mice. Differential cell analyses and myeloperoxidase assays for quantification of neutrophils showed a significantly reduced recruitment of neutrophils into the microenvironment of the parasites in immunized Gαi2−/− mice. However, cell transfer studies demonstrated that neutrophils from Gαi2−/− mice are competent in killing larvae. These data demonstrate that Gαi2 signaling events are not required for the development of the protective immune responses against S. stercoralis; however, Gαi2 is essential for the recruitment of neutrophils required for host-dependent killing of larvae.
Wound Complications in Elective Orthopaedics: Are Current British National Data Relevant?
Authors: Cloke DJ , Partington PF
Published: January 2007

INTRODUCTION

The UK Nosocomial Infection National Surveillance Service (NINSS) collects data on surgical wound infection in a variety of procedures, including arthroplasty, to allow comparison between institutions.

PATIENTS AND METHODS

We have compared the results of a 6-month data collection by NINSS within our department with our own grading system of wound complications in elective arthroplasty surgery.

RESULTS

In this period, NINSS has reported one wound infection in our patients. However, we have recorded five patients who were returned to theatre for wound debridement, and yielded positive cultures from multiple specimens. Seven patients received antibiotic therapy alone for wound problems.

CONCLUSIONS

We present our wound grading system as suitable for the collection of data on wound complications in elective orthopaedic surgery.
Functional Effects of Monoclonal Antibodies to the Purified Amino-Terminal Extracellular Domain of the Human Ca2+ Receptor
Authors: Hu Jianxin , Reyes-Cruz Guadalupe , Goldsmith Paul K , Gantt Nicole M , Miller Jeffery L , Spiegel Allen M
Published: January 2007

We generated three functionally unique monoclonal antibodies to the purified human CaR extracellular domain. Flow cytometry studies of chimeric receptors localized their epitopes to lobe 2 of the VFT domain. These results lead us to propose a mechanism for the functional effects of these antibodies.

Introduction: The human Ca2+ receptor (CaR), which plays a central role in the regulation of [Ca2+]0 homeostasis, has a distinctively large extracellular domain that consists of a bilobed Venus flytrap (VFT) domain, involved in agonist binding, and a cysteine-rich domain. Functional antibodies that specifically bind to this domain would have therapeutic potential and could be used as a tool to gain insights into receptor activation as well.

Materials and Methods: We generated three monoclonal antibodies (mAbs), 7F8, 5C8, and 1A8, to the purified human CaR extracellular domain. Functional characterization of these antibodies included Ca2+ stimulation of phosphoinositide hydrolysis to examine effects of intact or protease digested antibodies on sensitivity of the receptor to extracellular Ca2+ and flow cytometry assay of binding of the antibodies to HEK-293 cells expressing chimeric receptors to map antibody epitopes.

Results: We found these mAbs specifically recognize native but not denatured human CaR or homologous native Fugu CaR. Sensitivity of the human CaR to extracellular calcium was increased by binding of 5C8 but decreased by binding of 1A8. A chimeric receptor FCFCF, with lobe 2 region of the human CaR VFT domain in the Fugu CaR backbone, bound all three mAbs, and the sensitivity of this chimeric CaR to extracellular Ca2+ was also increased by binding of 5C8 and decreased by binding of 1A8.

Conclusions: The epitopes of these mAbs reside in the lobe 2 region of the human CaR VFT domain. 5C8 might activate the receptor by facilitating closure and/or rotation of the VFT domains on agonist binding, whereas 1A8 might inhibit the receptor by impeding such agonist-induced conformational changes. Recombinant antibodies with antigen binding domains of 5C8 and 1A8 could be useful in the treatment of hyperparathyroidism and osteoporosis, respectively.
ATP Release Mediates Fluid Flow–Induced Proliferation of Human Bone Marrow Stromal Cells
Authors: Riddle Ryan C , Taylor Amanda F , Rogers Jennifer R , Donahue Henry J
Published: January 2007

Oscillatory fluid flow induced the vesicular release of ATP from human BMSCs that directly contributes to the induction of BMSC proliferation. Degrading extracellular nucleotides prevents fluid flow–induced increases in intracellular calcium concentration, the activation of calcineurin, and the nuclear translocation of NFAT.

Introduction: Regulation of bone cell activity by autocrine/paracrine factors is a well-established mechanism by which skeletal homeostasis is regulated by mechanical signals. The release of extracellular nucleotides in particular has been shown to induce many of the responses thought to be necessary for load-induced bone formation. In these studies, we examined the effect of oscillatory fluid flow on the release of ATP from bone marrow stromal cells (BMSCs) and the effect of ATP release on BMSC proliferation and intracellular calcium signaling pathways.

Materials and Methods: BMSCs were exposed to oscillatory fluid flow, and the concentration of ATP in conditioned media samples was determined using a luciferin:luciferase-based reaction. Western blot analysis was used to examine the expression of purinergic receptors. Using pharmacological antagonists of gap junction hemichannels and vesicular trafficking, we studied the mechanism of ATP release from BMSCs. Apyrase was used to study the effect of extracellular nucleotides on intracellular calcium concentration, calcineurin activity, and nuclear factor of activated T cells (NFAT) nuclear translocation.

Results and Conclusions: Fluid flow exposure induced the flow rate–dependent release of ATP from BMSCs that was attenuated by treatment with monensin and N-ethylmaleimide, suggesting a vesicular mechanism. Treating BMSCs with ATP, but not other nucleotides, increased cellular proliferation. Moreover, extracellular ATP was a prerequisite for fluid flow–induced increases in intracellular calcium concentration, activation of calcineurin, the nuclear translocation of NFATc1, and proliferation. These data indicate that ATP regulates not only osteoblastic and osteocytic cell behavior but also that of mesenchymal precursors and support our hypothesis that similar mechanotransduction mechanisms are activated by fluid flow in these cell types.
Two-Year Randomized Controlled Trial of Vitamin K1 (Phylloquinone) and Vitamin D3 Plus Calcium on the Bone Health of Older Women
Authors: Bolton-Smith Caroline , McMurdo Marion ET , Paterson Colin R , Mole Patricia A , Harvey Julia M , Fenton Steven T , Prynne Celia J , Mishra Gita D , Shearer Martin J
Published: January 2007

Dietary supplementation with vitamin K1, with vitamin D3 and calcium or their combination, was examined in healthy older women during a 2-year, double-blind, placebo-controlled trial. Combined vitamin K with vitamin D plus calcium was associated with a modest but significant increase in BMC at the ultradistal radius but not at other sites in the hip or radius.

Introduction: The putative beneficial role of high dietary vitamin K1 (phylloquinone) on BMD and the possibility of interactive benefits with vitamin D were studied in a 2-year double-blind, placebo-controlled trial in healthy Scottish women ≤60 years of age.

Materials and Methods: Healthy, nonosteoporotic women (n = 244) were randomized to receive either (1) placebo, (2) 200 μg/day vitamin K1, (3) 10 μg (400 IU) vitamin D3 plus 1000 mg calcium/day, or (4) combined vitamins K1 and D3 plus calcium. Baseline and 6-month measurements included DXA bone mineral scans of the hip and wrist, markers of bone turnover, and vitamin status. Supplementation effects were tested using multivariate general linear modeling, with full adjustment for baseline and potential confounding variables.

Results: Significant bone mineral loss was seen only at the mid-distal radius but with no significant difference between groups. However, women who took combined vitamin K and vitamin D plus calcium showed a significant and sustained increase in both BMD and BMC at the site of the ultradistal radius. Serum status indicators responded significantly to respective supplementation with vitamins K and D. Over 2 years, serum vitamin K1 increased by 157% (p < 0.001), the percentage of undercarboxylated osteocalcin (%GluOC) decreased by 51% (p < 0.001), serum 25-hydroxyvitamin D [25(OH)D] increased by 17% (p < 0.001), and PTH decreased by 11% (p = 0.049).

Conclusions: These results provide evidence of a modest synergy in healthy older women from nutritionally relevant intakes of vitamin K1 together with supplements of calcium plus moderate vitamin D3 to enhance BMC at the ultradistal radius, a site consisting of principally trabecular bone. The substantial increase in γ-carboxylation of osteocalcin by vitamin K may have long-term benefits and is potentially achievable by increased dietary intakes of vitamin K rather than by supplementation.
Simultaneous Visualization of Multiple Antigens with Tyramide Signal Amplification using Antibodies from the same Species
Authors: Tóth Zsuzsanna E. , Mezey Éva
Published: January 2007

After immunohistochemistry (IHC) began to be used routinely, a number of investigators worked on methods for staining multiple molecules in the same tissue sections or cells. Achieving this goal was not easy, however. One reason for this is that the majority of primary antibodies used in IHC reactions are raised in rabbits, and recognizing signals from two different rabbit antibodies is not trivial. Thus, all of the protocols described to date have serious limitations. Here we report a simple, quick, and inexpensive solution to the problem. It has two major advantages over existing methods. First, by using antibodies from the same host, two or more antigens can be visualized in the same section with commercially available fluorescent dyes. Second, because the technique relies on signal amplification, both rare and abundant antigens can be detected.
The c-kit receptor protein in the testis of green frog Rana esculenta: seasonal changes in relationship to testosterone titres and spermatogonial proliferation
Authors: Raucci Franca , Di Fiore Maria Maddalena
Published: January 2007

The green frog Rana esculenta is a seasonal breeder. The cyclic changes between almost arrested and highly activated spermatogenesis offer an ideal model to study basic mechanisms of spermatogenesis. In this study, we demonstrated, to our knowledge for the first time, c-kit receptor positive cells in the testis of this amphibian. The presence of c-kit receptor protein was confirmed by western blotting (Wb) analyses carried out in the testis during all the three main phases of the sexual cycle. The antibody recognized a band of about 150 kDa that was correlated with the positive staining in the germinal epithelium. The immunolabelling for c-kit receptor, evaluated by immunohistochemistry (IHC), was localized in I and II spermatogonia (SPG), in I and II spermatocytes, in both elongating spermatids and spermatozoa and in the Leydig cells. Furthermore, c-kit expression showed a seasonal pattern connected with both testicular and plasma profiles of testosterone during the reproductive cycle. The highest expression of c-kit receptor occurred during the reproductive period, when the testis exhibited the maximum concentration of testosterone. In this period, the mitotic activity of germ cell, assessed by both Wb and IHC analyses for proliferating cell nuclear antigen (PCNA), was intensive. Indeed, during the post-reproductive period, testosterone titres were the lowest and the expression of both PCNA and c-kit receptor protein in the testis, although present, is minor when compared with the reproductive phase. This evidence suggests that cell division can continue sufficiently to accumulate SPG for the next spring, when new germinal cells undergo multiplication. Finally, during the pre-reproductive period, testosterone levels begin to increase and mitotic activity of germinal epithelium is comparably enhanced. These events seem to precede the period of maximum stimulated spermatogonial proliferation, i.e. the reproductive period. These results suggest that the c-kit receptor may play a role in germ cell proliferation and provide a basis for future detailed investigation of regulatory factors of the proliferation of SPG.
Adiposity associated rise in leptin impairs ovarian activity during winter dormancy in Vespertilionid bat, Scotophilus heathi
Authors: Srivastava Raj Kamal , Krishna Amitabh
Published: January 2007

The aim of the study was to evaluate the seasonal variation in serum leptin levels in a natural population of the female bat, Scotophilus heathi and their relationship to the changes in the body mass, serum insulin level, and ovarian activity. Circulating leptin level varied significantly over the season and correlated positively with the changes in body mass, and circulating insulin and androstenedione (A4) levels. Circulating leptin concentrations showed two peaks; one coincides with the maximum fat accumulation prior to winter dormancy, whereas the second shorter peak coincides with late pregnancy. The in vivo study in S. heathi showed that the increased circulating leptin level during winter dormancy coincides with the decreased expression of ovarian steroidogenic acute regulatory (StAR) protein, and low circulating estradiol (E2) level. At the same time, increased circulating leptin level coincides with increased expression of ovarian insulin receptor and high circulating A4 level. The low circulating leptin level during preovulatory period coincides with the increase in StAR protein but decrease in insulin receptor protein. The in vitro study confirmed the in vivo observations of inhibitory effect of leptin on LH induced StAR expression and E2 production, whereas the stimulatory effect of leptin (high dose) on LH induced expression of insulin receptor protein and A4 production. However, pharmacological dose of leptin produced inhibitory effect on the expression of insulin receptor protein. The results of the present study thus suggest that high circulating leptin level during winter dormancy promotes adiposity and impairs ovarian activity by suppressing StAR-mediated E2 production as well as by enhancing insulin receptor-mediated A4 synthesis thereby contributing anovulatory condition of delayed ovulation in S. heathi.