bluuebunny/crossref_metadata_2025 huggingface dataset:
Simultaneous surgical treatment of ruptured abdominal aortic aneurysm and acute carotide occlusive disease
Authors: Maksimovic Z.V. , Jakovljevic N. , Putnik S. , Jadranin D. , Markovic D. , Koncar I.
Published: July 2009

Combined rupture of abdominal aortic aneurysm and acute thrombosis of internal carotid artery is extremely rare but fatal combination resulting in high mortality rate. Presented case, shows successfully performed simultaneous surgery of ruptured abdominal aortic aneurysm and acute cerebrovascular insult caused by thrombosis of carotid artery in 81 year-old male. Post operative course was uneventfull. At 24 months follow up patient was in good condition, with full neurological recovery. Simultaneous surgical treatment of acute occlusive carotid disease and ruptured abdominal aortic aneurysm (RAAA) seems to be the only life saving procedure for this rare, but very complicated condition. To our knowledge, this is the first reported successful simultaneous surgical treatment of RAAA and acute thrombosis of internal carotid artery.
MHD heat and mass diffusion flow by natural convection past a surface embedded in a porous medium
Authors: Chaudhary R.C. , Jain Arpita
Published: July 2009

This paper presents an analytical study of the transient hydromagnetic natural convection flow past a vertical plate embedded in a porous medium, taking account of the presence of mass diffusion and fluctuating temperature about time at the plate. The governing equations are solved in closed form by the Laplace-transform technique. The results are obtained for temperature, velocity, penetration distance, Nusselt number and skin-friction. The effects of various parameters are discussed on the flow variables and presented by graphs.
Health Care Disparities and Diabetes Care: Practical Considerations for Primary Care Providers
Authors: White Richard O. , Beech Bettina M. , Miller Stephania
Published: July 2009

IN BRIEF

Disparities in diabetes care are prevalent in the United States. This article provides an overview of these disparities and discusses both potential causes and efforts to address them to date. The authors focus the discussion on aspects relevant to the patient-provider dyad and provide practical considerations for the primary care provider's role in helping to diminish and eliminate disparities in diabetes care.
Contingent Negative Variation under Competitive Situations
Authors: Matsumoto Sayaka , Sakuma Haruo
Published: July 2009

Participants high and low in competitiveness completed a reaction-time task with a warning stimulus designed to elicit contingent negative variation, competing on reaction speed with a visible or invisible opponent to identify what affects contingent negative variation amplitude under more critical competitive situations. For participants low in competitiveness, contingent negative variation was larger and reaction time (RT) was shorter when winning a trial and competing with a visible opponent. For those high in competitiveness, contingent negative variation was larger under competitive situations with a visible opponent than with an invisible one, although no difference was found in RT. These findings suggest that contingent negative variation amplitude under competitive situations reflects not only motor preparation but also other psychological processes such as awareness of an opponent.
Some Factors in Sanctions for Unsportsmanlike Behavior of Players and Coaches in Youth Soccer
Authors: Olmedilla Aurelio , Lozano Francisco J. , Ato Manuel , de los Fayos Enrique Garcés , Ortega Enrique
Published: July 2009

Reasons and motives for sanctions imposed on players and coaches in youth soccer were examined to evaluate frequency and type of infraction by competition category (Under 12, 13–14, 15–16, and 17–18 years). Analysis of the first 30% of competitions yielded 1,202 sanctions of 340 teams with 6,120 players and 340 coaches. For older groups, the number of sanctions for aggressive conduct by the players was significantly higher; frequency of sanctions imposed on the coaches for disrespect also was significantly higher, and those for aggression were higher although not significantly so; the number of sanctions for disrespect by players was not different. Transgressions of the game rules recorded by officials are a valid representation of a pedagogical factor important for coaches and players. Implementing informative programs for knowledge and conduct of rules is suggested.
Effect of Four Voluntary Regulated Yoga Breathing Techniques on Grip Strength
Authors: Joshi Meesha , Telles Shirley
Published: July 2009

Bilateral hand-grip strength was studied in 21 male volunteers ( M age = 25.6 yr., SD = 5.2). All were assessed before and after five practice sessions of 20 min. duration: right-nostril yoga breathing, left-nostril yoga breathing, alternate-nostril yoga breathing, breath awareness, and a no-intervention session. Data were analyzed with analyses of variance and an analysis of variance using the no-breath awareness control condition as a covariate. There were no significant changes. The left-hand-grip strength reduced after left-nostril yoga breathing. However, findings were not considered significant, so methodological issues in yoga research which could contribute to null findings and even mask actual changes were discussed.
Taste Discrimination after Separate Pre-Exposure and Test Sessions
Authors: Begoñatortolero María , Acosta María Gabriela , Espinet Alfredo
Published: July 2009

The effect of previous exposure on discrimination of two flavored solutions sharing a common taste was investigated in a pilot experiment. These solutions were at the limit of discrimination and the pre-exposure and test phases took place on different days. The results showed that mere pre-exposure (i.e., in absence of feedback) facilitates subsequent discrimination of same or different pairs of solutions. This result is in some aspects opposite to those reported recently by Dwyer and colleagues. This discrepancy is discussed analyzing the procedural differences observed between these studies.
Assessing Effectiveness of Various Auditory Warning Signals in Maintaining Drivers' Attention in Virtual Reality-Based Driving Environments
Authors: Lin Chin-Teng , Huang Teng-Yi , Liang Wen-Chieh , Chiu Tien-Ting , Chao Chih-Feng , Hsu Shang-Hwa , Ko Li-Wei
Published: July 2009

Drivers' fatigue contributes to traffic accidents, so drivers must maintain adequate alertness. The effectiveness of audio alarms in maintaining driving performance and characteristics of alarms was studied in a virtural reality-based driving environment. Response time to the car's drifting was measured under seven conditions: with no warnings and with continuous warning tones (500 Hz, 1750 Hz, and 3000 Hz), and with tone bursts at 500 Hz, 1750 Hz, and 3000 Hz. Analyses showed the audio warning signals significantly improved driving. Further, the tones' spectral characteristics significantly influenced the effectiveness of the warning.
The Preliminary Development of Computer-Assisted Assessment of Chinese Handwriting Performance
Authors: Chang Shao-Hsia , Yu Nan-Ying , Shie Jung-Jiun
Published: July 2009

This paper describes a pilot study investigating an assessment for Chinese handwriting performance. In an attempt to computerize the existing Tseng Handwriting Problem Checklist (Tseng Checklist), this study employed MATLAB to develop a computer program entitled the Chinese Handwriting Assessment Program (CHAP) to be used for the evaluation of handwriting performance. Through a template-matching approach, the program processed each character by using size-adjustable standard models to calculate the two-dimensional cross-correlation coefficient of a template and a superimposed handwritten character. The program measured the size control, spacing, alignment, and the average resemblance between standard models and handwritten characters. The results of the CHAP's test-retest reliability showed that the high correlation coefficients (from .81 to .94) were statistically significant. Correlations between each CHAP and Tseng Checklist item were statistically significant. As these assessment tools for handwriting performance are required for quantitative and qualitative aspects, the integration of the two tools is a promising means for accomplishing a handwriting performance assessment.
Use of the Quality of Life Inventory for Measuring Quality of Life Changes in an Inpatient Psychiatric Population
Authors: Angstman Sarah , Schuldberg David , Harris Kari Jo , Cochran Bryan , Peterson Polly
Published: July 2009

This study measured self-reported quality of life at two time points for 50 diagnostically heterogeneous patients in a state-funded psychiatric hospital and evaluated the Quality of Life Inventory for assessing changes over inpatient treatment. Participants completed the Quality of Life Inventory after admission and before discharge. Improvement occurred in overall scores during participants' hospital stays. Analysis of domains showed improvements in satisfaction with health and self-esteem. The inventory appears a useful tool for evaluating outcomes of psychiatric inpatient treatment from a patient perspective.
Preliminary Psychometric Data for a Portuguese Scale to Assess History of Depressive Symptomatology with a College Student Sample
Authors: Campos Rui C. , Gonçlalves Bruno , Thalbourne Michael
Published: July 2009

A Portuguese questionnaire was developed to assess the history of depressive symptoms. The Depressive History Questionnaire was based on the Depressive Experience Subscale from the Thalbourne Manic Depressiveness Scale, which was translated into Portuguese. The Depressive History Questionnaire was administered to 459 college students. Female students scored significantly higher than male students. Cronbach alpha was .64. Principal component analysis confirmed that the questionnaire measures only one dimension. Confirmatory factor analysis provided support for the fit of the one-factor model. The Depressive History Questionnaire correlated positively and significantly with the Portuguese versions of both the Beck Depression Inventory–II and the Depressive Personality Disorder Inventory.
Developing and Testing a Student-Focussed Teaching Evaluation Survey for University Instructors
Authors: Ginns Paul , Barrie Simon
Published: July 2009

This paper describes a process for developing a student-focussed survey to gather teaching- and learning-related feedback from university students and examines the psychometric properties of a short survey for confidential feedback to lecturers in higher education regarding teaching. Analyses were performed at the level of individual respondents and on teacher-average responses. Principal component and exploratory factor analyses at both levels indicated a single underlying lecturing effectiveness factor. Scale scores had high internal consistency. The items and subsequent scale were also consistent in terms of interrater reliability, i.e., the average consistency of ratings of an individual lecturer. Finally, at both levels of analysis, strong correlations between responses to each item and an overall rating provided support for the concurrent validity of the items. These analyses provide initial evidence of the suitability of the survey for gathering confidential student feedback on lecturing effectiveness.
Perceptions of Paranoid Thoughts in a Nonclinical Group of College Students
Authors: Yamauchi Takashi , Sudo Anju , Tanno Yoshihiko
Published: July 2009

Researchers have focused on the distinction between paranoid and social anxious thoughts for eliciting characteristics of paranoid thoughts in greater detail, which may aid theoretical development and understanding of persecutory delusions with regard to continuity between nonclinical and clinical symptoms. This is a report of characteristics of paranoid thoughts compared to social anxious thoughts in a sample of 128 college students. Nine dimensions concerning how individuals perceive their paranoid and social anxious thoughts were assessed as self-ratings for each on resistance, distress, absurdity, conviction, corrigibility, controllability, perception of intended harm, anger, and frequency. These dimensions for the two thoughts were generally independent of each other. Analyses suggested that paranoid thoughts might be characterized by higher distress, absurdity, corrigibility, perception of intended harm, and anger, and by lower conviction compared to social anxious thoughts in this nonclinical group.
Personality Correlates of Financial Behavior
Authors: Yang Bijou , Lester David , Spinella Marcello
Published: July 2009

In a sample of 98 students, scores for extraversion, neuroticism, psychoticism, and a Lie scale were associated with financial behavior, with Lie subscale scores providing the majority of the significant but weak associations.
Mental Health Problems of Men Attending District- Level Clinical Psychology Services in South Africa
Authors: Evans Dylan J. , Pillay Anthony L.
Published: July 2009

Over a 1-yr. period, 70 men attended district level clinical psychology services in Msunduzi, South Africa. The mean age was 35.9 yr., and 80% had secondary education. Only 65.7% attended of their own accord. 51% were unemployed, 71.4% had financial problems, 44.3% admitted to substance abuse, 74.3% reported relationship problems, and 14.3% admitted to being violent toward their partners, suicidal ideation was the commonest referral problem, while mood disorder was the most frequent diagnosis. Clinicians estimated that 75.7% of these men had low self-esteem. 45.8% (34) perceived their partner as disengaged, enmeshed, or oppressive.
The Hero Concept: Self, Family, and Friends who are Brave, Honest, and Hopeful
Authors: Staats Sara , Wallace Heidi , Anderson Tara , Gresley Jamee , Hupp Julie M. , Weiss Elizabeth
Published: July 2009

The concept of the hero is pervasive and enduring, extending across time, culture, and age. Although an influential schema, the hero has not been empirically examined in depth. Heroic exemplars given by students and community members were examined, and the hypotheses that individuals with high Heroism scores are more hopeful and report higher Coping than individuals with low Heroism scores were also tested. Participants reported similar depictions of heroes and heroic acts; the prototypic hero being a family member, and the most common act exemplified as averting physical harm to others. Quantitative results suggest that individuals high on Heroism scores are more hopeful and cope better than individuals low on Heroism scores. Results indicate that heroism is experienced in everyday life, and a model is proposed.
Overt and Covert Narcissism in Poland and the Netherlands
Authors: Zondag Hessel J. , van Halen Cor , Wojtkowiak Joanna
Published: July 2009

This article reports a study of the relation between narcissism as a personality characteristic and the cultural dimension of individualism/collectivism. Participants from a more collectivistic society (Poland; n = 167) were compared with participants from a more individualistic society (The Netherlands; n = 156). Two dimensions of narcissism were distinguished: overt and covert. The cultural tendency for narcissism was measured by comparing average scores on both types of narcissism in both countries, as well as by the meaning that overt and covert narcissism seems to have for psychological well-being. More specifically, the correlations were compared among both types of narcissism and depression and meaning of life. In the Polish sample, the average score on covert narcissism was higher. In the Dutch sample, on the other hand, depression and meaning of life were significantly related to covert narcissism.
Social and Cultural Influences among Mexican Border Entrepreneurs
Authors: Bretones Francisco Díaz , Cappello Héctor M. , Garcia Pedro A.
Published: July 2009

Social and cultural conditions (including U.S. border and inland influence, role models within the family, and educational background) which affect locus of control and achievement motivation among Mexican entrepreneurs were explored among 64 selected entrepreneurs in two Mexican towns, one on the Mexico-U.S. border, the other located inland. Analyses showed that the border subsample scored higher on External locus of control; however, in both subsamples the father was an important element in the locus of control variable and the entrepreneur status. No statistically significant mean difference was noted for achievement motivation. Practical applications and limitations are discussed.
Computer-Assisted Instruction in Concept Development of Six-Year-Old Children
Authors: Ayhan Aynur Bütün , Aral Neriman
Published: July 2009

Effects of a 15-wk. computer-assisted course or regular instruction on concept development by 6-yr.-old kindergarten children in Ankara ( M age of sample = 66.0 mo., SD = 4.6; M age of girls = 65.0 mo., SD = 4.4; M age of boys = 66.0 mo., SD = 4.5). Children were assigned to two groups of 40 (Experimental group: 18 girls and 22 boys; M girls' age = 65.3 mo., SD = 3.7, M boys' age = 67.1 mo., SD = 4.1; Control group: 21 girls, 19 boys, M girls' age = 64.9 mo., SD = 5.01, M boys' age = 66.7 mo., SD = 5.1). All were given the Bracken Basic Concept Scale–Revised and a general information form. Mean posttest scores in concept development for the group given computer-assisted training were statistically significantly higher.
Influence of Identity versus Oddity Pretraining on Symmetric Matching to Sample
Authors: Boelens Harrie , Schenk Jacqueline
Published: July 2009

Identity and oddity matching tasks were designed for different groups of 5-yr.-old children. The presentation of tasks continued until all children had shown evidence of appropriate generalization to new stimuli (i.e., generalized identity matching or generalized oddity from sample). All children then received training on an arbitrary matching-to-sample task. Finally, tests of reflexivity and symmetry in responding were carried out in three consecutive sessions. The children in the Identity group showed reflexivity and symmetry in responses on all three tests; the children in the Oddity group showed oddity in responses on all tests, and a gradual increase in symmetry of responses across tests. These results provide evidence against special versions of multiple-exemplar and reinforcement contingency accounts of stimulus equivalence. Versions of the accounts to explain the findings are discussed.
Internal Consistency Reliability of the Wisc–IV among Primary School Students
Authors: Ryan Joseph J. , Glass Laura A. , Bartels Jared M.
Published: July 2009

Internal consistency reliabilities of the WISC–IV subtest and index scores were estimated for a sample of 76 primary school students from a small Midwestern community. Means for age and Full Scale IQ were 8.2 yr. ( SD = 2.3) and 110.5 ( SD = 11.7), respectively. Internal consistency reliabilities were compared with those for the WISC–IV standardization sample of 200. The range of reliabilities for the subtests was from .76 for Picture Concepts to .94 for Arithmetic and from .92 for Perceptual Reasoning Index to .96 for Verbal Comprehension Index and Full Scale IQ. The Full Scale IQ internal consistency reliability is comparable to that of the standardization sample. However, in all but one instance the reliabilities were greater than those of the normative sample.
The Relationship of Body Image to Body Mass Index and Binge Eating: The Role of Cross-Situational Body Image Dissatisfaction versus Situational Reactivity
Authors: Saules Karen K. , Collings Amy S. , Wiedemann Ashley A. , Fowler Shannon L.
Published: July 2009

Although body image is often conceptualized as a trait, there is growing recognition of situational influences. It was hypothesized that college women whose body image was more reactive to situational influences would be more likely to experience adverse weight-related outcomes, including obesity and binge eating behavior. In a pilot study, vignettes were rated to yield a range of situational body image ratings, and the three vignettes that captured the full range (lowest, median, and highest ratings) were used in the main study. In the main study, 138 female undergraduates ( M = 19.5 yr., SD = 1.9; 74.6% “White or Caucasian”) completed a survey that included the Questionnaire on Eating and Weight Patterns–Revised. They also provided Body Image State Scale ratings in response to three vignettes drawn from the pilot study. Body image “reactivity” was defined as the range over which body image scores varied for a given participant (standard deviation of the means). Contrary to predictions, overall body dissatisfaction across situations—but not situational reactivity—was related to higher BMI, greater likelihood of binge eating, and higher depression. Results suggest when body image dissatisfaction is relatively impervious to situational influences, it may be a risk factor for disordered eating behavior, whereas body image dissatisfaction that is responsive to situational influences appears to be less pathognomonic.
Ecology and Drug Use: Universal Predictors across Time and Place
Authors: Brook Judith S. , Brook David W. , Kats Nataliya , Arencibia-Mireles Orlando , Finch Stephen J.
Published: July 2009

The interrelation of ecological and psychosocial risk factors and adolescent marijuana use is examined in this three-sample longitudinal data analysis. Participants included (a) white children from the northeast of the USA, (b) African-American and Puerto Rican adolescents from New York City, and (c) adolescents living in Colombia, South America. Adolescents were interviewed in their homes. Independent measures were from the ecological, personality, peer, and family domains. Logistic regression analysis showed that the majority of ecological variables was related to adolescent marijuana use. Hierarchical regression analysis demonstrated that the ecological domain was directly and indirectly related to adolescent marijuana use (via the family, peer, and personality domains). Intervention programs should focus on adolescents' unique ecological settings while targeting universal risk factors (e.g., low ego integration, low parental identification) which predict adolescents' marijuana use. Similarities among the ecological predictors of adolescents' marijuana use in three samples, across time and place, allow a more universal approach to the prevention of substance use.
Are the Blood Transfusion Safe!
Authors: Mahmud Z
Published: July 2009

doi: 10.3329/jafmc.v5i1.2838JAFMC Bangladesh. Vol 5, No 1 (June) 2009 pp.1-2
Incidence of Common Transfusion Transmitted Diseases Among Blood Donors
Authors: Ahmed Musleh Uddin , Begum Hosne Ara , Hossain Tozammel , Chakraborty Prodipesh
Published: July 2009

Transfusion transmitted diseases are one of the major health problem in Bangladesh. This study was carried out among 12,270 voluntary and directed donors in the transfusion medicine department of Khulna Medical College Hospital (KMCH), a teaching hospital of southern Bangladesh during the period from 1st July 2007 to 30th June 2008 to see the incidence of HIV, HCV, HBV, Syphilis & Malaria. All were voluntary and relative/directed donors. No professional donors had taken part in this donation system. Blood samples were collected in sterile dry plain test tube after predonation consent. Serum of each donor was collected by proper centrifugation within 6 hours of collection. Tests of all the samples were done within 24 hours of collection. The methods used were latex agglutination Immunochromatographic test (ICT) and reconfirmed by ELISA techniques. For malaria thick and thin film studies under microscope were done. On analyzing the results, 171 (1.39%) were found positive for HBsAg, 03 (0.024%) were positive for anti HCV, 01 was positive for anti HIV (0.008%). None found positive for Malarial parasite (MP) none were reactive for RPR test. Donation from professional blood donors are completely stopped in the transfusion medicine unit of KMCH. Mandatory screening of donated blood should be done for HIV, HBV, HCV, Syphilis and Malaria to reduce their transmission by transfusion. Key Words: Transfusion transmitted diseases, Blood donors.   doi: 10.3329/jafmc.v5i1.2840 JAFMC Bangladesh. Vol 5, No 1 (June) 2009 pp.4-6
A Marine Sulfate-Reducing Bacterium Producing Multiple Antibiotics: Biological and Chemical Investigation
Authors: Zhang Yi , Mu Jun , Gu Xiaojie , Zhao Chenyan , Wang Xiaoliang , Xie Zeping
Published: July 2009

A marine sulfate-reducing bacterium SRB-22 was isolated by means of the agar shake dilution method and identified as Desulfovibrio desulfuricans by morphological, physiological and biochemical characteristics and 16S rDNA analysis. In the bioassay, its extract showed broad-spectrum antimicrobial activity using the paper disc agar diffusion method. This isolate showed a different antimicrobial profile than either ampicillin or nystatin and was found to produce at least eight antimicrobial components by bioautography. Suitable fermentation conditions for production of the active constituents were determined to be 28 day cultivation at 25 °C to 30 °C with a 10% inoculation ratio. Under these conditions, the SRB-22 was fermented, extracted and chemically investigated. So far an antimicrobial compound, mono-n-butyl phthalate, and an inactive compound, thymine, have been isolated and characterized.
Gold film-catalysed benzannulation by Microwave-Assisted, Continuous Flow Organic Synthesis (MACOS)
Authors: Shore Gjergji , Tsimerman Michael , Organ Michael G
Published: July 2009

Methodology has been developed for laying down a thin gold-on-silver film on the inner surface of glass capillaries for the purpose of catalysing benzannulation reactions. The cycloaddition precursors are flowed through these capillaries while the metal film is being heated to high temperatures using microwave irradiation. The transformation can be optimized rapidly, tolerates a wide number of functional groups, is highly regioselective, and proceeds in good to excellent conversion.
Caveolae Facilitate but Are Not Essential for Platelet-Activating Factor-Mediated Calcium Mobilization and Extracellular Signal-Regulated Kinase Activation
Authors: Poisson Caroline , Rollin Simon , Véronneau Steeve , Bousquet Simon M. , Larrivée Jean-François , Le Gouill Christian , Boulay Guylain , Stankova Jana , Rola-Pleszczynski Marek
Published: July 2009

Certain proteins, including receptors and signaling molecules, are known to be enriched in caveolae and lipid rafts. Caveolin-1, the major structural protein of caveolae, specifically interacts with many signaling molecules and, thus, caveolae and lipid rafts are often seen as preassembled signaling platforms. A potential binding site for caveolin-1 is present in the platelet-activating factor receptor (PAFR) sequence, and many downstream signaling components of PAFR activation preferentially localize in caveolae. The aim of this study was to investigate whether the PAFR was localized in caveolae/lipid raft domains and, if so, what would be the significance of such localization for PAFR signaling. In this study, we demonstrate that PAFR localizes within membrane microdomains, in close proximity to caveolin-1 in living cells, with potential interaction through a caveolin-1-binding sequence in the PAFR C terminus. Caveolin-1, however, is not essential for PAFR localization in lipid rafts. Disruption of caveolae/lipid rafts with methyl-β-cyclodextrin markedly reduced PAF-triggered inositol phosphate production and cytosolic calcium flux, suggesting that PAFR signaling through the Gαq protein was critically dependent on integrity of lipid rafts and/or caveolae. Interestingly, whereas in caveolin-1-expressing cells lipid raft disruption markedly decreased PAFR-mediated activation of the ERK/MAPK pathway, in cells lacking caveolae, such as leukocytes, lipid raft disruption had either the same inhibitory effect (Ramos B cells) or no effect (monocytes) on PAFR capacity to signal through the ERK/MAPK pathway. In conclusion, PAFR appears to localize within caveolae or lipid rafts in different cell types, and this location may be important for specific signaling events.
Blocking TNF-α Attenuates Aneurysm Formation in a Murine Model
Authors: Xiong Wanfen , MacTaggart Jason , Knispel Rebecca , Worth Jennifer , Persidsky Yuri , Baxter B. Timothy
Published: July 2009

Abdominal aortic aneurysm (AAA) is one of a number of diseases associated with a prominent inflammatory cell infiltrate and local destruction of structural matrix macromolecules. This chronic infiltrate is predominately composed of macrophages and T lymphocytes. Activated macrophages produce a variety of cytokines, including TNF-α. Elevated levels of TNF-α were observed in patients with AAA, suggesting that TNF-α may play a role in the pathogenic mechanisms of AAA. In the present study, we investigated the role of TNF-α in AAA formation. By studying a murine aneurysm model, we found that both mRNA and protein levels of TNF-α were increased in aneurysm tissue compared with normal aortic tissues. Therefore, we tested the response of mice lacking expression of TNF-α. These mice were resistant to aneurysm formation. Our results show that TNF-α deficiency attenuates matrix metalloproteinase (MMP) 2 and MMP-9 expression and macrophage infiltration into the aortic tissue. These data suggest that TNF-α plays a central role in regulating matrix remodeling and inflammation in the aortic wall leading to AAA. In addition, we investigated the pharmacological inhibition of AAA. A Food and Drug Administration-approved TNF-α antagonist, infliximab, inhibited aneurysm growth. Our data also show that infliximab treatment attenuated elastic fiber disruption, macrophage infiltration, and MMP-2 and MMP-9 expression in aortic tissue. This study confirms that a strategy of TNF-α antagonism may be an important therapeutic strategy for treating AAA.
Aberrant Selection and Function of Invariant NKT Cells in the Absence of AP-1 Transcription Factor Fra-2
Authors: Lawson Victoria J. , Maurice Diane , Silk Jonathan D. , Cerundolo Vincenzo , Weston Kathleen
Published: July 2009

The transcription factors mediating the development of CD1d-restricted invariant NKT (iNKT) cells remain incompletely described. Here, we show that loss of the AP-1 transcription factor Fra-2 causes a marked increase in the number of both thymic and peripheral iNKT cells, without affecting the development of other T-lineage cells. The defect is cell-autonomous and is evident in the earliest iNKT precursors. We find that iNKT cells expressing the lower affinity TCRVβ8 are proportionally overrepresented in the absence of Fra-2, indicating altered selection of iNKT cells. There is also widespread dysregulation of AP-1-directed gene expression. In the periphery, mature Fra-2-deficient iNKT cells are able to participate in an immune response, but they have an altered response to Ag, showing increased expansion and producing increased amounts of IL-2 and IL-4 compared with their wild-type counterparts. Unusually, naive Fra-2-deficient T cells also rapidly produce IL-2 and IL-4 upon activation. Taken together, these data define Fra-2 as necessary for regulation of normal iNKT cell development and function, and they demonstrate the central role played by the AP-1 family in this lineage.
Novel Generation Mycobacterial Adjuvant Based on Liposome-Encapsulated Monomycoloyl Glycerol from Mycobacterium bovis Bacillus Calmette-Guérin
Authors: Andersen Claire A. Swetman , Rosenkrands Ida , Olsen Anja W. , Nordly Pernille , Christensen Dennis , Lang Roland , Kirschning Carsten , Gomes Jessica M. , Bhowruth Veemal , Minnikin David E. , Besra Gurdyal S. , Follmann Frank , Andersen Peter , Agger Else Marie
Published: July 2009

The immunostimulatory activity of lipids associated with the mycobacterial cell wall has been recognized for several decades and exploited in a large variety of different adjuvant preparations. Previously, we have shown that a mycobacterial lipid extract from Mycobacterium bovis bacillus Calmette-Guérin delivered in cationic liposomes was a particular efficient Th1-inducing adjuvant formulation effective against tuberculosis. Herein, we have dissected the adjuvant activity of the bacillus Calmette-Guérin lipid extract showing that the majority of the activity was attributable to the apolar lipids and more specifically to a single lipid, monomycoloyl glycerol (MMG), previously also shown to stimulate human dendritic cells. Delivered in cationic liposomes, MMG induced the most prominent Th1-biased immune response that provided significant protection against tuberculosis. Importantly, a simple synthetic analog of MMG, based on a 32 carbon mycolic acid, was found to give rise to comparable high Th1-biased responses with a major representation of polyfunctional CD4 T cells coexpressing IFN-γ, TNF-α, and IL-2. Furthermore, comparable activity was shown by an even simpler monoacyl glycerol analog, based on octadecanoic acid. The use of these synthetic analogs of MMG represents a promising new strategy for exploiting the immunostimulatory activity and adjuvant potential of components from the mycobacterial cell wall without the associated toxicity issues observed with complex mycobacterial preparations.
Leukotriene B4 Potentiates CpG Signaling for Enhanced Cytokine Secretion by Human Leukocytes
Authors: Gaudreault Éric , Gosselin Jean
Published: July 2009

TLRs are known to be important in innate host defense against a variety of microbial infections. In particular, TLR9 has been associated with immune defense against different foreign organisms by recognition of unmethylated DNA sequences. In this report, we provide evidence that leukotriene B4 (LTB4) has the capacity to modulate TLR9 expression on human neutrophils. The effect of LTB4 was found to be specific, because related leukotrienes such as LTC4 and LTD4 or neutrophil agonists IL-8 and C5a failed to modulate TLR9 expression in neutrophils. Using fluorochrome-tagged CpG DNA, we observed that LTB4 treatment also increased TLR9 ligand binding in neutrophils. Moreover, LTB4 stimulation potentiates CpG-mediated signaling via an endosome-independent mechanism in human neutrophils, leading to enhanced secretion of proinflammatory cytokines. The increase in cytokine secretion by LTB4 following CpG stimulation of neutrophils was associated with the activation of TGF-β-activated kinase (TAK-1) as well as p38 and c-Jun (JNK) kinases. In contrast, in PBMC LTB4 leads to an increase in cytokine secretion following CpG stimulation but via a MyD88- and endosome-dependent mechanism. As observed in neutrophils, PBMC stimulation with LTB4 in the presence of CpG also results in enhanced TAK-1, p38, and JNK phosphorylation/activation. These data provide new evidence underlying the immunomodulatory properties of LTB4 leading to antimicrobial defense.
The Peroxisome Proliferator-Activated Receptor γ Agonist Pioglitazone Improves Cardiometabolic Risk and Renal Inflammation in Murine Lupus
Authors: Zhao Wenpu , Thacker Seth G. , Hodgin Jeffrey B. , Zhang Hongyu , Wang Jeffrey H. , Park James L. , Randolph Ann , Somers Emily C. , Pennathur Subramaniam , Kretzler Matthias , Brosius Frank C. , Kaplan Mariana J.
Published: July 2009

Individuals with systemic lupus erythematosus (SLE) have a striking increase in the risk of premature atherosclerosis, a complication preceded by significant subclinical vascular damage. A proposed mechanism leading to accelerated vascular disease in SLE is an imbalance between vascular damage and repair, as patients with this disease display significant abnormalities in phenotype and function of endothelial progenitor cells. In addition, individuals with SLE have a higher incidence of insulin resistance which may further contribute to the increased cardiovascular risk. This study examined the role of the peroxisome proliferator activated receptor γ agonist pioglitazone in improving endothelial function, endothelial progenitor cell numbers and functional capacity, metabolic parameters, and disease activity in the lupus-prone murine model New Zealand Black/New Zealand White (NZB × NZW)F1. Ten-week-old prenephritic female NZB/NZW F1 mice were exposed to 10 or 25 mg/kg/day of oral pioglitazone or vehicle for 15 or 24 wk. Mice exposed to pioglitazone exhibited pronounced enhancement in endothelial-dependent vasorelaxation of thoracic aortas and in endothelial progenitor cell function, as assessed by the capacity of bone marrow-derived endothelial progenitor cells to differentiate into mature endothelial cells. Pioglitazone-treated mice showed improvement in insulin resistance, adipokine, and lipid profile. Kidneys from pioglitazone-treated mice showed significant decreases in immune complex deposition, renal inflammation, T cell glomerular infiltration, and intrarenal synthesis of TNF-α, IL-1β, and VCAM-1. These results indicate that peroxisome proliferator-activated receptor γ agonists could serve as important tools in the prevention of premature cardiovascular disease and organ damage in SLE.
Perturbation of the CD4 T Cell Compartment and Expansion of Regulatory T Cells in Autoimmune-Prone Lyn-Deficient Mice
Authors: Tsantikos Evelyn , Quilici Cathy , Harder Kenneth W. , Wang Bo , Zhu Hong-Jian , Anderson Gary P. , Tarlinton David M. , Hibbs Margaret L.
Published: July 2009

Regulatory T cells (Tregs) are a subset of T lymphocytes that are responsible for suppressing the function of other immune cells, and preventing potentially harmful autoimmune responses. Studies in autoimmune-prone mice and human autoimmune diseases have shown reduced Treg number or function as a causative factor for the apparent loss of tolerance that contributes to disease. We have found that Lyn-deficient mice, which develop high titers of autoantibodies with age, have a perturbed Treg compartment. Contrary to what has been observed in some strains of autoimmune-prone mice, aged Lyn-deficient mice have increased numbers of Tregs. This expansion occurs in the presence of elevated serum IL-2 and diminished TGF-β. Despite expansion of the Treg compartment, Lyn-deficient mice succumb at ∼1 year of age due to immune complex-mediated glomerulonephritis. We have shown that Lyn is not expressed in Tregs or indeed in any T cell subset, suggesting that the expansion and apparent functional deficiency in Tregs in Lyn-deficient mice is due to extrinsic factors rather than an intrinsic Treg defect. Indeed, using an in vivo colitis model, we have shown that Lyn-deficient Tregs can suppress inflammation. These results suggest that Tregs are expanding in Lyn-deficient mice in an effort to control the autoimmune disease but are simply overwhelmed by the disease process. This study highlights the role of the inflammatory setting in autoimmune disease and its consideration when contemplating the use of Tregs as an autoimmune therapy.
Regulation of Inflammatory Monocyte/Macrophage Recruitment from the Bone Marrow during Murine Cytomegalovirus Infection: Role for Type I Interferons in Localized Induction of CCR2 Ligands
Authors: Crane Meredith J. , Hokeness-Antonelli Kirsten L. , Salazar-Mather Thais P.
Published: July 2009

Monocytes/macrophages are critical early innate immune responders during murine CMV (MCMV) infection. It has been established that inflammatory monocyte/macrophages are released from the bone marrow and into the peripheral blood before entry into infected tissue sites. We previously reported a role for IFN-α/β in promotion of CCR2-mediated recruitment of monocyte/macrophages into the liver in response to MCMV infection. However, the mechanisms that support the migration of monocyte/macrophages from the bone marrow and into the peripheral blood under conditions of MCMV infection have not been elucidated. Herein, we demonstrate an accumulation of monocyte/macrophages in the bone marrow of MCMV-infected CCR2-deficient mice, whereas circulating monocyte/macrophages are profoundly diminished. The CCR2 ligands MCP-1, MCP-3, and MCP-5 are detected in bone marrow and in serum from MCMV-infected mice. Furthermore, bone marrow leukocytes from naive mice produce high levels of MCP-1 and MCP-5, and moderate levels of MCP-3, when stimulated with recombinant IFN-α in culture. We identify bone marrow F4/80+ cells as major producers of MCP-1, MCP-3, and MCP-5. Moreover, induction of CCR2 ligands is dependent on IFN-α/β-mediated signals and MCMV infection. Taken together, the results reveal a critical role for inflammatory cytokines in stimulating production of CCR2-binding chemokines from F4/80+ cells in the bone marrow, and they suggest that local production of chemokines supports monocyte/macrophage egress from the bone marrow into the blood during a virus infection.
Human Neutrophils Kill Streptococcus pneumoniae via Serine Proteases
Authors: Standish Alistair J. , Weiser Jeffrey N.
Published: July 2009

Neutrophils, or polymorphonuclear leukocytes, comprise a crucial component of innate immunity, controlling bacterial and fungal infection through a combination of both oxidative and nonoxidative mechanisms. Indeed, neutrophils are believed to play an important role in controlling infection caused by the major human pathogen Streptococcus pneumoniae. However, the method by which neutrophils kill the pneumococcus as well as other Gram-positive bacteria, is not fully understood. We investigated human neutrophil killing of the pneumococcus in a complement-dependent opsonophagocytic assay. In contrast to other Gram-positive organisms, inhibition of the NADPH oxidase did not affect killing of S. pneumoniae. Supernatant from degranulated neutrophils killed the pneumococcus, suggesting a role for granular products. When neutrophil granule proteases were inhibited with either a protease mixture, or specific serine protease inhibitors 4-(2-Aminoethyl)benzenesulfonylfluoride and diisopropylfluorophosphate, killing by neutrophils was inhibited in a manner that correlated with increased intracellular survival. All three compounds inhibited intracellular activity of the three major neutrophil serine proteases: elastase, cathepsin G, and proteinase 3. Additionally, purified elastase and cathepsin G were sufficient to kill S. pneumoniae in a serine protease dependent-manner in in vitro assays. Inhibition studies using specific inhibitors of these serine proteases suggested that while each serine protease is sufficient to kill the pneumococcus, none is essential. Our findings show that Gram-positive pathogens are killed by human neutrophils via different mechanisms involving serine proteases.
Interactions between Innate Antiviral and Atopic Immunoinflammatory Pathways Precipitate and Sustain Asthma Exacerbations in Children
Authors: Subrata Lily S. , Bizzintino Joelene , Mamessier Emilie , Bosco Anthony , McKenna Katherine L. , Wikström Matthew E. , Goldblatt Jack , Sly Peter D. , Hales Belinda J. , Thomas Wayne R. , Laing Ingrid A. , LeSouëf Peter N. , Holt Patrick G.
Published: July 2009

Severe asthma exacerbations in children requiring hospitalization are typically associated with viral infection and occur almost exclusively among atopics, but the significance of these comorbidities is unknown. We hypothesized that underlying interactions between immunoinflammatory pathways related to responses to aeroallergen and virus are involved, and that evidence of these interactions is detectable in circulating cells during exacerbations. To address this hypothesis we used a genomics-based approach involving profiling of PBMC subpopulations collected during exacerbation vs convalescence by microarray and flow cytometry. We demonstrate that circulating T cells manifest the postactivated “exhausted” phenotype during exacerbations, whereas monocyte/dendritic cell populations display up-regulated CCR2 expression accompanied by phenotypic changes that have strong potential for enhancing local inflammation after their recruitment to the atopic lung. Notably, up-regulation of FcεR1, which is known to markedly amplify capacity for allergen uptake/presentation to Th2 effector cells via IgE-mediated allergen capture, and secondarily programming of IL-4/IL-13-dependent IL-13R+ alternatively activated macrophages that have been demonstrated in experimental settings to be a potent source of autocrine IL-13 production. We additionally show that this disease-associated activation profile can be reproduced in vitro by cytokine exposure of atopic monocytes, and furthermore that IFN-α can exert both positive and negative roles in the process. Our findings suggest that respiratory viral infection in atopic children may initiate an atopy-dependent cascade that amplifies and sustains airway inflammation initiated by innate antiviral immunity via harnessing underlying atopy-associated mechanisms. These interactions may account for the unique susceptibility of atopics to severe viral-induced asthma exacerbations.
Sphingosine 1-Phosphate Enhances Fcγ Receptor-Mediated Neutrophil Activation and Recruitment under Flow Conditions
Authors: Florey Oliver , Haskard Dorian O.
Published: July 2009

Sphingosine 1-phosphate (S1P) is a bioactive phospholipid that is released by platelets and endothelial cells and has been implicated in diverse biological functions. We hypothesized that S1P may influence immune complex-mediated polymorphonuclear neutrophil activation. Using flow cytometry and fluorescence spectrometry, we found that exogenous addition of S1P led to an enhanced polymorphonuclear neutrophil Fcγ receptor-mediated rise in intracellular Ca2+ and reactive oxygen species generation in a pertussis toxin-independent manner, while having only a small effect by itself. Thus, S1P amplifies a positive feedback loop where Fcγ receptor-mediated rises in Ca2+ and reactive oxygen species are interdependent, with reactive oxygen species acting to increase tyrosine phosphorylation and activity of upstream signaling intermediates. S1P augmentation of Fcγ receptor signaling translates to downstream functional consequences, including shape change and recruitment to endothelial surfaces coated with suboptimal levels of immune complexes. Taken together, S1P from activated platelets or endothelial cells may serve to amplify leukocyte recruitment and tissue injury at sites of immune complex deposition in vasculitis.
Helios Deficiency Has Minimal Impact on T Cell Development and Function
Authors: Cai Qi , Dierich Andrée , Oulad-Abdelghani Mustapha , Chan Susan , Kastner Philippe
Published: July 2009

Helios is a member of the Ikaros family of zinc finger transcription factors. It is expressed mainly in T cells, where it associates with Ikaros-containing complexes and has been proposed to act as a rate-limiting factor for Ikaros function. Overexpression of wild-type or dominant-negative Helios isoforms profoundly alters αβ T cell differentiation and activation, and endogenous Helios is expressed at strikingly high levels in regulatory T cells. Helios has also been implicated as a tumor suppressor in human T cell acute lymphoblastic leukemias. These studies suggest a central role for Helios in T cell development and homeostasis, but whether this protein is physiologically required in T cells is unclear. We report herein that inactivation of the Helios gene by homologous recombination does not impair the differentiation and effector cell function of αβ and γδ T cells, NKT cells, and regulatory T cells. These results suggest that Helios is not essential for T cells, and that its function can be compensated for by other members of the Ikaros family.