bluuebunny/crossref_metadata_2025 huggingface dataset:
Public relations and organizational justice: More fairness or just more cooperation?
Authors: Simmons Peter , Walsh Barbara
Published: April 2012

This article brings together two established fields of organizational study, organizational justice (OJ) and public relations (PR), in a search for potential benefits. The ‘fair process effect’ says that people tend to behave more cooperatively and prosocially when they perceive fairness in a situation, and less cooperatively when they perceive unfairness. Scholars have stressed the potential benefits of understanding perceptions of fairness in a range of contexts including policing, sport refereeing, management and teaching. Some have also challenged OJ scholars to use that field’s understanding of what people find to be fair to better help the victims of injustice.

The article reports that PR and OJ have developed bodies of knowledge that enhance organizations’ capacity to influence change for greater fairness, but both fields have been criticized because their knowledge has more often been applied to increasing the perception of fairness (resulting in greater stakeholder cooperation with organizations and their decisions), than to increasing fair outcomes for a range of stakeholders. The article also shows that PR could benefit in several ways from a deeper understanding of OJ, and that OJ could be very usefully integrated in tertiary PR and professional inservice courses. First, OJ may provide a meta-language and evidence basis for planning, framing and evaluating organizational communication and processes that would help PR focus on the frames and drivers of fairness. Second, PR, like OJ, needs a better understanding of power if it is to recognize subtle forms of domination and exercise influence that advances fairness for the most vulnerable. Third, OJ highlights the importance of independence in decision making if those affected by decisions are to trust decision makers and perceive decisions to be fair. Stakeholder mistrust limits PR agency and capacity to advance fairness, but independence would represent a profound shift from the existing paradigm of relations that PR practitioners have with organizations, as employees or consultants. The article introduces PR to OJ’s impressive body of empirical evidence from organizations, and sophisticated theories and models to frame and clarify concepts for advancing practice and scholarship of fairness. Although it may be tempting to apply the power of procedural and interactional justice effects to influence perceptions of fairness and reactions to privately determined decisions, the article cautions that stakeholders will best be served where PR ensures that multiple voices are heard and acted on in matters of distribution.
A public relations identity for the 2010s
Authors: Ihlen Øyvind , Verhoeven Piet
Published: April 2012

New voices are being heard and new questions are being asked within the field of public relations. However, in its present multifaceted state, public relations research is still struggling with recurring questions regarding academic and practical contributions. This position article presents some common starting points for a public relations identity for the 2010s aiming to preserve both consistency and multiplicity. We argue that public relations should be studied as a social activity in its own right and that it must be understood in relation to its societal context. Furthermore, we point to some concepts (trust, legitimacy, understanding and reflection) that are crucial to understanding public relations practice. We also argue that issues of power, behavior, and language have to be dealt with if public relations is to be taken seriously as an academic field. Building on these ideas we make some suggestions for empirical research. Finally, we propose, on a philosophical level, to develop a critical realist framework in order to study public relations scientifically.
Interpreting ethics: Public relations and strong hermeneutics
Authors: Fawkes Johanna
Published: April 2012

This article suggests that public relations’ inadequate engagement with the complexities of ethical theory has contributed to public loss of trust in its activities. Instead of blaming this on publics, communicators could take more responsibility for their professional ethics. The author suggests that a hermeneutic approach to ethics opens up a new area for debate in the field. Public relations ethics have traditionally drawn on the major approaches of deontology (Kant) and consequentialism (Bentham and Mill), with marginal reference to the more recent revival of Aristotelian virtue ethics (MacIntyre, 1984), an approach that shifts attention from ethical action to ethical agent. Thus discussion of ethics in public relations literature (Fitzpatrick and Bronstein, 2006; S. A. Bowen, 2007; McElreath, 1996) concentrates on rational approaches to ethical decision making, based (respectively) in marketplace theory, Kantian approaches or systems theory. In these and other writings, there is an emphasis, as is common in approaches to professional ethics, on external rule-based ethics rather than attempts to focus on inner processes to assess ethical implications of practice. This article argues that as concepts of professionalism shift and buckle under global economic and social pressures, it might be timely to look less to systems and more to human experience for ethical guidance. A hermeneutic approach, drawing on the philosophy of interpretation developed in recent decades by thinkers such as Gadamer, Habermas and Riceour, offers an alternative, inner, path to an ethics drawn from the search for shared meaning.

The article starts with a brief overview of the current state of public relations ethics, suggesting a reliance on somewhat superficial codes for guidance and the absence of reflexivity in ethical debates; it then introduces concepts from hermeneutics and its main schools or approaches, with a particular focus on hermeneutic ethics. Finally, the article links the two topics to show how ‘strong’ hermeneutic ethics might contribute to greater reflexivity in public relations ethics. It aims to shift the ethical debate away from notional reliance on codes and external guidance towards a deeper ethic. The approach taken is broadly critical (Hall, 1980; Heath, 1992) and is itself interpretative, making the article doubly-hermeneutic (Giddens, 1984) in both form and content.
Intravascular Sonography Assessment of a Type III Endoleak of an Aortic Endograft
Authors: Augustyn Joseph S.
Published: April 2012

Abdominal aortic aneurysm (AAA) is a common disease in today’s older population. When AAAs grow large, the risk for rupture becomes high, and the AAA should be treated. It can be treated in one of two ways: open or endovascular repair. With endovascular repair, an endograft is placed within the aorta using angiographic guidance to exclude the AAA. Intravascular sonography (IVUS) can be used as an adjunct to angiography for the endovascular repair. The endograft must then be routinely followed for complications such as endoleak. This case report identifies a symptomatic type III endoleak and describes how IVUS is used in conjunction with computed tomography and angiography to treat type III endoleaks.
Splenic Abscess Detection and Monitoring Using Sonography
Authors: McKinney Elizabeth Ruzicka
Published: April 2012

The finding of a splenic abscess is rare, with only 500 to 600 cases ever having been reported internationally. Prior to the advent of sonography and computed tomography, the survival rate for an individual with a splenic abscess was 0%. Present-day real-time imaging with sonography allows for accurate diagnosis of an abscess in the spleen versus rupture, hematoma, splenomegaly, or cyst within the spleen or left kidney. Until recently, the prescribed treatment was splenectomy. The increased understanding of splenic abscess etiology and advancements in pharmacology have allowed the treatment to progress from surgical removal of the entire spleen to draining the abscess using fine-needle aspiration with the use of strong broad-spectrum intravenous antibiotics.
Sister Vascular Anomalies in the Nongravid Uterus
Authors: Gillis Katherine , Davie Katherine
Published: April 2012

Uterine arteriovenous malformation and arteriovenous fistula are rare vascular lesions that have only recently been described in literature. They are two differentials in reproductive-age women with acute onset of abnormal vaginal bleeding. The sonographic and clinical presentation of these two pathologies can be both varied in appearance and impossible to distinguish from each other. However, a detailed history along with specific sonographic investigation using color and pulse-wave Doppler, as well as a transvaginal scanning technique, can lead to strong suspicion of these vascular malformities. A successful sonogram can provide essential evidence to justify further investigation with a more invasive angiography procedure. This will not only confirm a diagnosis but also give important information regarding the size and exact location of the lesion. These facts will help the interventional radiologist and treating physician decide if different types of embolization are possible or if hysterectomy is necessary.
Cell-autonomous role of TGFβ and IL-2 receptors in CD4+ and CD8+ inducible regulatory T-cell generation during GVHD
Authors: Sawamukai Norifumi , Satake Atsushi , Schmidt Amanda M. , Lamborn Ian T. , Ojha Priti , Tanaka Yoshiya , Kambayashi Taku
Published: April 2012

FoxP3+ regulatory T cells (Tregs) suppress GVHD while preserving graft-versus-tumor effects, making them an attractive target for GVHD therapy. The donor-derived Treg pool can potentially be derived from the expansion of preexisting natural Tregs (nTregs) or from de novo generation of inducible Tregs (iTregs) from donor Tconvs in the transplantation recipient. Using an MHC-mismatched model of acute GVHD, in the present study we found that the Treg pool was comprised equally of donor-derived nTregs and iTregs. Experiments using various combinations of T cells from wild-type and FoxP3-deficient mice suggested that both preexisting donor nTregs and the generation of iTregs in the recipient mice contribute to protection against GVHD. Surprisingly, CD8+FoxP3+ T cells represented approximately 70% of the iTreg pool. These CD8+FoxP3+ T cells shared phenotypic markers with their CD4+ counterparts and displayed suppressive activity, suggesting that they were bona fide iTregs. Both CD4+ and CD8+ Tregs appeared to be protective against GVHD-induced lethality and required IL-2 and TGFβ receptor expression for their generation. These data illustrate the complex makeup of the donor-derived FoxP3+ Treg pool in allogeneic recipients and their potential role in protection against GVHD.
Emergence of T cells that recognize nonpolymorphic antigens during graft-versus- host disease
Authors: Rangarajan Hemalatha , Yassai Maryam , Subramanian Hariharan , Komorowski Richard , Whitaker Megan , Gorski Jack , Drobyski William R.
Published: April 2012

Chronic GVHD is a major cause of morbidity and mortality in allogeneic stem cell transplantation recipients and typically develops from antecedent acute GVHD. In contrast to acute GVHD, chronic GVHD has much broader tissue involvement and clinical manifestations that bear striking similarity to what is observed in autoimmune diseases. How autoimmunity arises out of alloimmunity has been a longstanding unresolved issue. To address this question, in the present study, we performed a comprehensive analysis of the clonotypic T-cell response using complementary murine models that simulate what occurs during the transition from acute to chronic GVHD. These studies revealed repertoire skewing and the presence of high-frequency clonotypes that had undergone significant in vivo expansion, indicating that GVHD-associated autoimmunity was characterized by antigen-driven expansion of a limited number of T-cell clones. Furthermore, we observed that T cells with identical TCRβ CDR3 nucleotide sequences were capable of recognizing donor and host antigens, providing evidence that the loss of self-tolerance during acute GVHD leads to the emergence of self-reactive donor T cells that are capable of recognizing nonpolymorphic tissue or commensally derived antigens. These data provide a mechanistic framework for how autoimmunity develops within the context of preexisting GVHD and provide additional insight into the pathophysiology of chronic GVHD.
The risk of tuberculosis in transplant candidates and recipients: a TBNET consensus statement
Authors: Bumbacea Dragos , Arend Sandra M. , Eyuboglu Fusun , Fishman Jay A. , Goletti Delia , Ison Michael G. , Jones Christine E. , Kampmann Beate , Kotton Camille N. , Lange Christoph , Ljungman Per , Milburn Heather , Morris Michele I. , Muller Elmi , Muñoz Patricia , Nellore Anoma , Rieder Hans L. , Sester Urban , Theodoropoulos Nicole , Wagner Dirk , Sester Martina
Published: April 2012

Tuberculosis (TB) is a possible complication of solid organ and hematopoietic stem cell transplantation. The identification of candidates for preventive chemotherapy is an effective intervention to protect transplant recipients with latent infection withMycobacterium tuberculosisfrom progressing to active disease. The best available proxy for diagnosing latent infection withM. tuberculosisis the identification of an adaptive immune response by the tuberculin skin test or an interferon-γ basedex vivoassay. Risk assessment in transplant recipients for the development of TB depends on, among other factors, the locally expected underlying prevalence of infection withM. tuberculosisin the target population. In areas of high prevalence, preventive chemotherapy for all transplant recipients may be justified without immunodiagnostic testing while in areas of medium and low prevalence, preventive chemotherapy should only be offered to candidates with positiveM. tuberculosis-specific immune responses. The diagnosis of TB in transplant recipients can be challenging. Treatment of TB is often difficult due to substantial interactions between anti-TB drugs and immunosuppressive medications. This management guideline summarises current knowledge on the prevention, diagnosis and treatment of TB related to solid organ and hematopoietic stem cell transplantation and provides an expert consensus on questions where scientific evidence is still lacking.
Cord blood angiogenic progenitor cells are decreased in bronchopulmonary dysplasia
Authors: Baker Christopher D. , Balasubramaniam Vivek , Mourani Peter M. , Sontag Marci K. , Black Claudine P. , Ryan Sharon L. , Abman Steven H.
Published: April 2012

Bronchopulmonary dysplasia (BPD), the chronic lung disease of prematurity, is associated with impaired vascular and alveolar growth. Antenatal factors contribute to the risk for developing BPD by unclear mechanisms. Endothelial progenitor cells, such as angiogenic circulating progenitor cells (CPCs) and late-outgrowth endothelial colony-forming cells (ECFCs), may contribute to angiogenesis in the developing lung. We hypothesise that cord blood angiogenic CPCs and ECFCs are decreased in preterm infants with moderate and severe BPD.

We quantified ECFCs and the CPC/nonangiogenic-CPC ratio (CPC/non-CPC) in cord blood samples from 62 preterm infants and assessed their relationships to maternal and perinatal risk factors as well as BPD severity. The CPC/non-CPC ratio and ECFC number were compared between preterm infants with mild or no BPD and those with moderate or severe BPD.

ECFC number (p<0.001) and CPC/non-CPC ratio (p<0.05) were significantly decreased in cord blood samples of preterm infants who subsequently developed moderate or severe BPD. Gestational age and birth weight were not associated with either angiogenic marker.

Circulating vascular progenitor cells are decreased in the cord blood of preterm infants who develop moderate and severe BPD. These findings suggest that prenatal factors contribute to late respiratory outcomes in preterm infants.
Paediatric patients with a tracheostomy: a multicentre epidemiological study
Authors: Pérez-Ruiz Estela , Caro Pilar , Pérez-Frías Javier , Cols Maria , Barrio Isabel , Torrent Alba , García Maria Ángeles , Asensio Oscar , Pastor Maria Dolores , Luna Carmen , Torres Javier , Osona Borja , Salcedo Antonio , Escribano Amparo , Cortell Isidoro , Gaboli Mirella , Valenzuela Alfredo , Álvarez Elena , Velasco Rosa , García Enrique
Published: April 2012

Changes in the indications for tracheostomy in children have led to the progressively greater involvement of the paediatric pulmonologist in the care of these patients. The aim of this study was to review the current profile of tracheostomised children in Spain.

We undertook a longitudinal, multicentre study over 2 yrs (2008 and 2009) of all patients aged between 1 day and 18 yrs who had a tracheostomy.

The study, involving 18 Spanish hospitals, included 249 patients, of whom 150 (60.2%) were <1 yr of age. The main indications for the procedure were prolonged ventilation (n=156, 62.6%), acquired subglottic stenosis (n=34, 13.6%), congenital or acquired craniofacial anomalies (n=25, 10%) and congenital airway anomalies (n=24, 9.6%). The most frequent underlying disorders were neurological diseases (n=126, 50.6%) and respiratory diseases (n=98, 39.3%). Over the 2-yr study period, 92 (36.9%) children required ventilatory support, and decannulation was achieved in 59 (23.7%). Complications arose in 117 patients (46.9%). Mortality attributed to the underlying condition was 12.5% and that related directly to the tracheostomy was 3.2%.

Respiratory complexity of tracheostomised children necessitates prolonged, multidisciplinary follow-up, which can often extend to adulthood.
Host response to mechanical ventilation for viral respiratory tract infection
Authors: Hennus Marije P. , Janssen Riny , Pennings Jeroen L.A. , Hodemaekers Hennie M. , Kruijsen Debby , Jansen Nicolaas J. , Meyaard Linde , van Vught Adrianus J. , Bont Louis J.
Published: April 2012

Respiratory syncytial virus (RSV) bronchiolitis causes severe respiratory tract infection in infants, frequently necessitating mechanical ventilatory support. However, life-saving, mechanical ventilation aggravates lung inflammation. We set up a model to dissect the host molecular response to mechanical ventilation in RSV infection. Furthermore, the response to induced hypercapnic acidosis, reported to dampen the inflammatory response to mechanical ventilation in non-infectious models, was assessed.

BALB/c mice were inoculated with RSV or mock-suspension and ventilated for 5 h on day 5 post inoculation.

Mechanical ventilation of infected mice resulted in enhanced cellular influx and increased concentrations of pro-inflammatory cytokines in the bronchoalveolar space. Microarray analysis showed that enhanced inflammation was associated with a molecular signature of a stress response to mechanical ventilation with little effect on the virus-induced innate immune response. Hypercapnic acidosis during mechanical ventilation of infected mice did not change host transcript profiles.

We conclude that mechanical ventilation during RSV infection adds a robust but distinct molecular stress response to virus-induced innate immunity activation, emphasising the importance of lung-protective mechanical ventilation strategies. Induced hypercapnic acidosis has no major effect on host transcription profiles during mechanical ventilation for RSV infection, suggesting that this is a safe approach to minimise ventilator-induced lung injury.
Extracellular matrix composition in COPD
Authors: Annoni Raquel , Lanças Tatiana , Yukimatsu Tanigawa Ryan , de Medeiros Matsushita Marcus , de Morais Fernezlian Sandra , Bruno Andreina , Fernando Ferraz da Silva Luiz , Roughley Peter J. , Battaglia Salvatore , Dolhnikoff Marisa , Hiemstra Pieter S. , Sterk Peter J. , Rabe Klaus F. , Mauad Thais
Published: April 2012

Extracellular matrix (ECM) composition has an important role in determining airway structure. We postulated that ECM lung composition of chronic obstructive pulmonary disease (COPD) patients differs from that observed in smoking and nonsmoking subjects without airflow obstruction.

We determined the fractional areas of elastic fibres, type-I, -III and -IV collagen, versican, decorin, biglycan, lumican, fibronectin and tenascin in different compartments of the large and small airways and lung parenchyma in 26 COPD patients, 26 smokers without COPD and 16 nonsmoking control subjects.

The fractional area of elastic fibres was higher in non-obstructed smokers than in COPD and nonsmoking controls, in all lung compartments. Type-I collagen fractional area was lower in the large and small airways of COPD patients and in the small airways of non-obstructed smokers than in nonsmokers. Compared with nonsmokers, COPD patients had lower versican fractional area in the parenchyma, higher fibronectin fractional area in small airways and higher tenascin fractional area in large and small airways compartments. In COPD patients, significant correlations were found between elastic fibres and fibronectin and lung function parameters.

Alterations of the major ECM components are widespread in all lung compartments of patients with COPD and may contribute to persistent airflow obstruction.
Thoracoscore fails to predict complications following elective lung resection
Authors: Bradley Amy , Marshall Andrea , Abdelaziz Mahmoud , Hussain Khalid , Agostini Paula , Bishay Ehab , Kalkat Maninder , Steyn Richard , Rajesh Pala , Dunn Janet , Naidu Babu
Published: April 2012

The Thoracoscore mortality risk model has been incorporated into the British Thoracic Society guidelines on the radical management of patients with lung cancer. The discriminative and predictive ability to predict mortality and post-operative pulmonary complications (PPCs) in this group of patients is uncertain.

A prospective observational study was carried out on all patients following lung resectionviathoracotomy in a regional thoracic centre over 42 months. 128 out of 703 subjects developed a PPC. 16 (2%) patients died in hospital. In a logistic regression analysis the Thoracoscore was not a significant predictor of mortality (OR 1.07, 95% CI 0.99–1.17; p=0.11) but was a significant predictor of PPCs (OR 1.08, 95% CI 1.03–1.13; p=0.002). However, the area under the receiver operator characteristic curve for the Thoracoscore was 0.68 (95% CI 0.56–0.80) for predicting mortality and 0.64 (95% CI 0.59–0.69) for PPCs, indicating limited discriminative ability.

In a logistic regression analysis, another risk model, the European Society Objective Score, was predictive of mortality (OR 1.43, 95% CI 1.11–1.83; p=0.006) and PPCs (OR 1.48, 95% CI 1.30–1.68; p<0.0001).

Therefore, Thoracoscore may have poor discriminative and predictive ability for mortality and PPCs following elective lung resection.
Modeling overdispersed longitudinal binary data using a combined beta and normal random-effects model
Authors: Kassahun Wondwosen , Neyens Thomas , Molenberghs Geert , Faes Christel , Verbeke Geert
Published: April 2012

Background

In medical and biomedical areas, binary and binomial outcomes are very common. Such data are often collected longitudinally from a given subject repeatedly overtime, which result in clustering of the observations within subjects, leading to correlation, on the one hand. The repeated binary outcomes from a given subject, on the other hand, constitute a binomial outcome, where the prescribed mean-variance relationship is often violated, leading to the so-called overdispersion.

Methods

Two longitudinal binary data sets, collected in south western Ethiopia: the Jimma infant growth study, where the child’s early growth is studied, and the Jimma longitudinal family survey of youth where the adolescent’s school attendance is studied over time, are considered. A new model which combines both overdispersion, and correlation simultaneously, also known as the combined model is applied. In addition, the commonly used methods for binary and binomial data, such as the simple logistic, which accounts neither for the overdispersion nor the correlation, the beta-binomial model, and the logistic-normal model, which accommodate only for the overdispersion, and correlation, respectively, are also considered for comparison purpose. As an alternative estimation technique, a Bayesian implementation of the combined model is also presented.

Results

The combined model results in model improvement in fit, and hence the preferred one, based on likelihood comparison, and DIC criterion. Further, the two estimation approaches result in fairly similar parameter estimates and inferences in both of our case studies. Early initiation of breastfeeding has a protective effect against the risk of overweight in late infancy (p = 0.001), while proportion of overweight seems to be invariant among males and females overtime (p = 0.66). Gender is significantly associated with school attendance, where girls have a lower rate of attendance (p = 0.001) as compared to boys.

Conclusion

We applied a flexible modeling framework to analyze binary and binomial longitudinal data. Instead of accounting for overdispersion, and correlation separately, both can be accommodated simultaneously, by allowing two separate sets of the beta, and the normal random effects at once.
De novo assembly and characterization of the root transcriptome of Aegilops variabilis during an interaction with the cereal cyst nematode
Authors: Xu De-Lin , Long Hai , Liang Jun-Jun , Zhang Jie , Chen Xin , Li Jing-Liang , Pan Zhi-Fen , Deng Guang-Bing , Yu Mao-Qun
Published: April 2012

Background

Aegilops variabilis No.1 is highly resistant to cereal cyst nematode (CCN). However, a lack of genomic information has restricted studies on CCN resistance genes in Ae. variabilis and has limited genetic applications in wheat breeding.

Results

Using RNA-Seq technology, we generated a root transcriptome at a sequencing depth of 4.69 gigabases of Ae. variabilis No. 1 from a pooled RNA sample. The sample contained equal amounts of RNA extracted from CCN-infected and untreated control plants at three time-points. Using the Trinity method, nearly 52,081,238 high-quality trimmed reads were assembled into a non-redundant set of 118,064 unigenes with an average length of 500 bp and an N50 of 599 bp. The total assembly was 59.09 Mb of unique transcriptome sequences with average read-depth coverage of 33.25×. In BLAST searches of our database against public databases, 66.46% (78,467) of the unigenes were annotated with gene descriptions, conserved protein domains, or gene ontology terms. Functional categorization further revealed 7,408 individual unigenes and three pathways related to plant stress resistance.

Conclusions

We conducted high-resolution transcriptome profiling related to root development and the response to CCN infection in Ae. variabilis No.1. This research facilitates further studies on gene discovery and on the molecular mechanisms related to CCN resistance.
Expression of CD39 on FoxP3+ T regulatory cells correlates with progression of HBV infection
Authors: Tang Yan , Jiang Li , Zheng Yanhua , Ni Bing , Wu Yuzhang
Published: April 2012

Background

Although it is known that regulatory T cells (Tregs) can suppress the function of effector T cells, and may contribute to impaired immune response, the precise role of Tregs during the course of hepatitis B virus (HBV) infection remains to be elucidated. A newly identified subset of the CD4+Foxp3+ Tregs, the CD39+ Tregs, has been associated with viral infections and autoimmune diseases. Therefore, we hypothesized that this discrete Treg subset may contribute to the chronic infection of HBV.

Results

Initial characterization studies of healthy peripheral CD39+FoxP3+CD4+ T cells revealed that the majority were CD45RA- Treg cells. Subsequent analysis of HBV-infected patients (38 asymptomatic HBV carriers (AsCs), 37 chronic active hepatitis B (CAH), 29 HBV-associated acute-on-chronic liver failure (ACLF)) and healthy individuals (25 controls) was conducted to assess association with HBV copy number and the liver injury marker alanine aminotransferase (ALT). A higher percentage of CD39+ Tregs was detected within the population of FoxP3+CD4+ T cells in peripheral blood of AsCs patients. Moreover, the percentage of CD39+ Tregs was significantly less in CAH and ACLF patients. The increased proportions of circulating CD39+ Tregs were positively correlated with serum viral load, but inversely correlated with serum ALT level.

Conclusion

These findings not only suggest that CD39+ Treg cells may be involved in HBV disease progression but also identify CD39+ Tregs as a dynamic immune regulatory cell population that may represent a new target of immunomodulatory therapeutic interventions.
QRS pattern and improvement in right and left ventricular function after cardiac resynchronization therapy: a radionuclide study
Authors: Domenichini Giulia , Burri Haran , Valzania Cinzia , Gavaruzzi Gilberto , Fallani Francesco , Biffi Mauro , Sunthorn Henri , Diemberger Igor , Martignani Cristian , Foulkes Huberdine , Fleury Eric , Boriani Giuseppe
Published: April 2012

Background

Predicting response to cardiac resynchronization therapy (CRT) remains a challenge. We evaluated the role of baseline QRS pattern to predict response in terms of improvement in biventricular ejection fraction (EF).

Methods

Consecutive patients (pts) undergoing CRT implantation underwent radionuclide angiography at baseline and at mid-term follow-up. The relationship between baseline QRS pattern and mechanical dyssynchrony using phase analysis was evaluated. Changes in left and right ventricular EF (LVEF and RVEF) were analyzed with regard to baseline QRS pattern.

Results

We enrolled 56 pts, 32 with left bundle branch block (LBBB), 4 with right bundle branch block (RBBB) and 20 with non-specific intraventricular conduction disturbance (IVCD). A total of 48 pts completed follow-up. LBBB pts had significantly greater improvement in LVEF compared to RBBB or non-specific IVCD pts (+9.6 ± 10.9% vs. +2.6 ± 7.6%, p = 0.003). Response (defined as ≥ 5% increase in LVEF) was observed in 68% of LBBB vs. 24% of non-specific IVCD pts (p = 0.006). None of the RBBB pts were responders. RVEF was significantly improved in LBBB (+5.0 ± 9.0%, p = 0.007), but not in non-specific IVCD and RBBB pts (+0.4 ± 5.8%, p = 0.76). At multivariate analysis, LBBB was the only predictor of LVEF response (OR, 7.45; 95% CI 1.80-30.94; p = 0.006), but not QRS duration or extent of mechanical dyssynchrony.

Conclusions

Presence of a LBBB is a marker of a positive response to CRT in terms of biventricular improvement. Pts with non-LBBB pattern show significantly less benefit from CRT than those with LBBB.
Metal ion levels in large-diameter total hip and resurfacing hip arthroplasty-Preliminary results of a prospective five year study after two years of follow-up
Authors: Maurer-Ertl W , Friesenbichler J , Sadoghi P , Pechmann M , Trennheuser M , Leithner A
Published: April 2012

Background

Metal-on-metal hip resurfacing is an alternative to metal-on-metal total hip arthroplasty, especially for young and physically active patients. However, wear which might be detected by increased serum ion levels is a matter of concern.

Methods

The aims of this preliminary study were to determine the raise of metal ion levels at 2-years follow-up in a prospective setting and to evaluate differences between patients with either resurfacing or total hip arthroplasty. Furthermore we investigated if the inclination of the acetabular component and the arc of cover would influence these findings. Therefore, 36 patients were followed prospectively.

Results

The results showed increments for Co and Cr in both implant groups. Patients treated with large-diameter total hip arthroplasty showed fourfold and threefold, respectively, higher levels for Co and Cr compared to the resurfacing group (Co: p < 0,001 and Cr: p = 0,005). Nevertheless, we observed no significant correlation between serum ion levels, inclination and arc of cover.

Discussion

In order to clarify the biologic effects of ion dissemination and to identify risks concerning long-term toxicity of metals, the exposure should be monitored carefully. Therefore, long-term studies have to be done to determine adverse effects of Co and Cr following metal-on-metal hip replacement.
The effect of saponins from Ampelozizyphus amazonicus Ducke on the renal Na+ pumps’ activities and urinary excretion of natriuretic peptides
Authors: Diniz Lúcio Ricardo Leite , Portella Viviane Gomes , Cardoso Flávia Magalhães , de Souza Aloa Machado , Caruso-Neves Celso , Cassali Geovanni Dantas , dos Reis Adelina Martha , Brandão MariadasGraçasLins , Vieira Maria Aparecida Ribeiro
Published: April 2012

Background

In a previous study, we showed that a saponin mixture isolated from the roots of Ampelozizyphus amazonicus Ducke (SAPAa D) reduces urine excretion in rats that were given an oral loading of 0.9 % NaCl (4 ml/100 g body weight). In the present study, we investigated whether atrial natriuretic peptides (ANP) and renal ATPases play a role in the SAPAa D- induced antidiuresis in rats.

Methods

To evaluate the effect of SAPAa D on furosemide-induced diuresis, Wistar rats (250-300 g) were given an oral loading of physiological solution (0.9 % NaCl, 4 ml/100 g body weight) to impose a uniform water and salt state. The solution containing furosemide (Furo, 13 mg/kg) was given 30 min after rats were orally treated with 50 mg/kg SAPAa D (SAPAaD + Furo) or 0.5 ml of 0.9 % NaCl (NaCl + Furo). In the SAPAaD + NaCl group, rats were pretreated with SAPAa D and 30 min later they received the oral loading of physiological solution. Animals were individually housed in metabolic cages, and urine volume was measured every 30 min throughout the experiment (3 h). To investigate the role of ANP and renal Na+ pumps on antidiuretic effects promoted by SAPAa D, rats were given the physiological solution (as above) containing SAPAa D (50 mg/kg). After 90 min, samples of urine and blood from the last 30 min were collected. Kidneys and atria were also removed after previous anesthesia. ANP was measured by radioimmunoassay (RIA) and renal cortical activities of Na+- and (Na+,K+)-ATPases were calculated from the difference between the [32P] Pi released in the absence and presence of 1 mM furosemide/2 mM ouabain and in the absence and presence of 1 mM ouabain, respectively.

Results

It was observed that SAPAa D inhibited furosemide-induced diuresis (at 90 min: from 10.0 ± 1.0 mL, NaCl + Furo group, n = 5, to 5.9 ± 1.0 mL, SAPAaD + Furo group n = 5, p < 0.05), increased both Na+-ATPase (from 25.0 ± 5.9 nmol Pi.mg-1.min-1, control, to 52.7 ± 8.9 nmol Pi.mg-1.min-1, p < 0.05) and (Na+,K+)-ATPase (from 47.8 ± 13.3 nmol Pi.mg-1.min-1, control, to 79.8 ± 6.9 nmol Pi .mg-1.min-1, p < 0.05) activities in the renal cortex. SAPAa D also lowered urine ANP (from 792 ± 132 pg/mL, control, to 299 ± 88 pg/mL, p < 0.01) and had no effect on plasma or atrial ANP.

Conclusion

We concluded that the SAPAa D antidiuretic effect may be due to an increase in the renal activities of Na+- and (Na+,K+)-ATPases and/or a decrease in the renal ANP.
Molecular network profiling of U373MG human glioblastoma cells following induction of apoptosis by novel marine-derived anti-cancer 1,2,3,4-tetrahydroisoquinoline alkaloids
Authors: Tabunoki Hiroko , Saito Naoki , Suwanborirux Khanit , Charupant Kornvika , Satoh Jun-ichi
Published: April 2012

Background

Glioblastoma is the most aggressive form of brain tumors showing resistance to treatment with various chemotherapeutic agents. The most effective way to eradicate glioblastoma requires the concurrent inhibition of multiple signaling pathways and target molecules involved in the progression of glioblastoma. Recently, we obtained a series of 1,2,3,4-tetrahydroisoquinoline alkaloids with potent anti-cancer activities, including ecteinascidin-770 (ET-770; the compound 1a) and renieramycin M (RM; the compound 2a) from Thai marine invertebrates, together with a 2’-N-4”-pyridinecarbonyl derivative of ET-770 (the compound 3). We attempted to characterize the molecular pathways responsible for cytotoxic effects of these compounds on a human glioblastoma cell line U373MG.

Methods

We studied the genome-wide gene expression profile on microarrays and molecular networks by using pathway analysis tools of bioinformatics.

Results

All of these compounds induced apoptosis of U373MG cells at nanomolar concentrations. The compound 3 reduced the expression of 417 genes and elevated the levels of 84 genes, while ET-770 downregulated 426 genes and upregulated 45 genes. RM decreased the expression of 274 genes and increased the expression of 9 genes. The set of 196 downregulated genes and 6 upregulated genes showed an overlap among all the compounds, suggesting an existence of the common pathways involved in induction of apoptosis. We identified the ErbB (EGFR) signaling pathway as one of the common pathways enriched in the set of downregulated genes, composed of PTK2, AKT3, and GSK3B serving as key molecules that regulate cell movement and the nervous system development. Furthermore, a GSK3B-specific inhibitor induced apoptosis of U373MG cells, supporting an anti-apoptotic role of GSK3B.

Conclusion

Molecular network analysis is a useful approach not only to characterize the glioma-relevant pathways but also to identify the network-based effective drug targets.
Anticonvulsant and analgesic activities of crude extract and its fractions of the defensive secretion from the Mediterranean sponge, Spongia officinalis
Authors: Dellai Afef , Mansour Hedi Ben , Clary-Laroche Audrey , Deghrigue Monia , Bouraoui Abderrahman
Published: April 2012

This study progresses in the direction of identifying component(s) from the Mediterranean sponge, Spongia officinalis with anticonvulsant and analgesic activities. We investigated the efficacy of crude extract and its semi-purified fractions (F1-F3) of the defensive secretion from Spongia officinalis for their in vivo anticonvulsant activity using the pentylenetetrazole (PTZ) seizure model and analgesic activity using the writhing test in mice. Among the series the crude extract exhibited interesting analgesic activity in a dose dependent manner. Similarly the fraction F2 showed a partial protection of mice from PTZ-induced seizure and interesting analgesic activity in a dose dependent manner. The purification and the determination of chemical structure(s) of compound(s) of this active fraction are under investigation.
A reinvestigation of somatic hypermethylation at the PTEN CpG island in cancer cell lines
Authors: Hesson Luke B , Packham Deborah , Pontzer Emily , Funchain Pauline , Eng Charis , Ward Robyn L
Published: April 2012

Background

PTEN is an important tumour suppressor gene that is mutated in Cowden syndrome as well as various sporadic cancers. CpG island hypermethylation is another route to tumour suppressor gene inactivation, however, the literature regarding PTEN hypermethylation in cancer is controversial. Furthermore, investigation of the methylation status of the PTEN CpG island is challenging due to sequence homology with the PTEN pseudogene, PTENP1. PTEN shares a CpG island promoter with another gene known as KLLN. Here we present a thorough reinvestigation of the methylation status of the PTEN CpG island in DNA from colorectal, breast, ovarian, glioma, lung and haematological cancer cell lines.

Results

Using a range of bisulphite-based PCR assays we investigated 6 regions across the PTEN CpG island. We found that regions 1-4 were not methylated in cancer cell lines (0/36). By allelic bisulphite sequencing and pyrosequencing methylation was detected in regions 5 and 6 in colorectal, breast and haematological cancer cell lines. However, methylation detected in this region was associated with the PTENP1 promoter and not the PTEN CpG island.

Conclusions

We show that methylation of the PTEN CpG island is a rare event in cancer cell lines and that apparent methylation most likely originates from homologous regions of the PTENP1 pseudogene promoter. Future studies should utilize assays that reliably discriminate between PTEN and PTENP1 to avoid data misinterpretation.
Glutathione S-transferase omega genes in Alzheimer and Parkinson disease risk, age-at-diagnosis and brain gene expression: an association study with mechanistic implications
Authors: Allen Mariet , Zou Fanggeng , Chai High Seng , Younkin Curtis S , Miles Richard , Nair Asha A , Crook Julia E , Pankratz V Shane , Carrasquillo Minerva M , Rowley Christopher N , Nguyen Thuy , Ma Li , Malphrus Kimberly G , Bisceglio Gina , Ortolaza Alexandra I , Palusak Ryan , Middha Sumit , Maharjan Sooraj , Georgescu Constantin , Schultz Debra , Rakhshan Fariborz , Kolbert Christopher P , Jen Jin , Sando Sigrid B , Aasly Jan O , Barcikowska Maria , Uitti Ryan J , Wszolek Zbigniew K , Ross Owen A , Petersen Ronald C , Graff-Radford Neill R , Dickson Dennis W , Younkin Steven G , Ertekin-Taner Nilüfer
Published: April 2012

Background

Glutathione S-transferase omega-1 and 2 genes (GSTO1, GSTO2), residing within an Alzheimer and Parkinson disease (AD and PD) linkage region, have diverse functions including mitigation of oxidative stress and may underlie the pathophysiology of both diseases. GSTO polymorphisms were previously reported to associate with risk and age-at-onset of these diseases, although inconsistent follow-up study designs make interpretation of results difficult. We assessed two previously reported SNPs, GSTO1 rs4925 and GSTO2 rs156697, in AD (3,493 ADs vs. 4,617 controls) and PD (678 PDs vs. 712 controls) for association with disease risk (case-controls), age-at-diagnosis (cases) and brain gene expression levels (autopsied subjects).

Results

We found that rs156697 minor allele associates with significantly increased risk (odds ratio = 1.14, p = 0.038) in the older ADs with age-at-diagnosis > 80 years. The minor allele of GSTO1 rs4925 associates with decreased risk in familial PD (odds ratio = 0.78, p = 0.034). There was no other association with disease risk or age-at-diagnosis. The minor alleles of both GSTO SNPs associate with lower brain levels of GSTO2 (p = 4.7 × 10-11-1.9 × 10-27), but not GSTO1. Pathway analysis of significant genes in our brain expression GWAS, identified significant enrichment for glutathione metabolism genes (p = 0.003).

Conclusion

These results suggest that GSTO locus variants may lower brain GSTO2 levels and consequently confer AD risk in older age. Other glutathione metabolism genes should be assessed for their effects on AD and other chronic, neurologic diseases.
Two structurally discrete GH7-cellobiohydrolases compete for the same cellulosic substrate fiber
Authors: Segato Fernando , Damasio André R L , Gonçalves Thiago Augusto , Murakami Mario T , Squina Fabio M , Polizeli MariadeLourdesTM , Mort Andrew J , Prade Rolf A
Published: April 2012

Background

Cellulose consisting of arrays of linear beta-1,4 linked glucans, is the most abundant carbon-containing polymer present in biomass. Recalcitrance of crystalline cellulose towards enzymatic degradation is widely reported and is the result of intra- and inter-molecular hydrogen bonds within and among the linear glucans. Cellobiohydrolases are enzymes that attack crystalline cellulose. Here we report on two forms of glycosyl hydrolase family 7 cellobiohydrolases common to all Aspergillii that attack Avicel, cotton cellulose and other forms of crystalline cellulose.

Results

Cellobiohydrolases Cbh1 and CelD have similar catalytic domains but only Cbh1 contains a carbohydrate-binding domain (CBD) that binds to cellulose. Structural superpositioning of Cbh1 and CelD on the Talaromyces emersonii Cel7A 3-dimensional structure, identifies the typical tunnel-like catalytic active site while Cbh1 shows an additional loop that partially obstructs the substrate-fitting channel. CelD does not have a CBD and shows a four amino acid residue deletion on the tunnel-obstructing loop providing a continuous opening in the absence of a CBD. Cbh1 and CelD are catalytically functional and while specific activity against Avicel is 7.7 and 0.5 U.mg prot-1, respectively specific activity on p NPC is virtually identical. Cbh1 is slightly more stable to thermal inactivation compared to CelD and is much less sensitive to glucose inhibition suggesting that an open tunnel configuration, or absence of a CBD, alters the way the catalytic domain interacts with the substrate. Cbh1 and CelD enzyme mixtures on crystalline cellulosic substrates show a strong combinatorial effort response for mixtures where Cbh1 is present in 2:1 or 4:1 molar excess. When CelD was overrepresented the combinatorial effort could only be partially overcome. CelD appears to bind and hydrolyze only loose cellulosic chains while Cbh1 is capable of opening new cellulosic substrate molecules away from the cellulosic fiber.

Conclusion

Cellobiohydrolases both with and without a CBD occur in most fungal genomes where both enzymes are secreted, and likely participate in cellulose degradation. The fact that only Cbh1 binds to the substrate and in combination with CelD exhibits strong synergy only when Cbh1 is present in excess, suggests that Cbh1 unties enough chains from cellulose fibers, thus enabling processive access of CelD.
Deficient expression of DNA repair enzymes in early progression to sporadic colon cancer
Authors: Facista Alexander , Nguyen Huy , Lewis Cristy , Prasad Anil R , Ramsey Lois , Zaitlin Beryl , Nfonsam Valentine , Krouse Robert S , Bernstein Harris , Payne Claire M , Stern Stephen , Oatman Nicole , Banerjee Bhaskar , Bernstein Carol
Published: April 2012

Background

Cancers often arise within an area of cells (e.g. an epithelial patch) that is predisposed to the development of cancer, i.e. a "field of cancerization" or "field defect." Sporadic colon cancer is characterized by an elevated mutation rate and genomic instability. If a field defect were deficient in DNA repair, DNA damages would tend to escape repair and give rise to carcinogenic mutations.

Purpose

To determine whether reduced expression of DNA repair proteins Pms2, Ercc1 and Xpf (pairing partner of Ercc1) are early steps in progression to colon cancer.

Results

Tissue biopsies were taken during colonoscopies of 77 patients at 4 different risk levels for colon cancer, including 19 patients who had never had colonic neoplasia (who served as controls). In addition, 158 tissue samples were taken from tissues near or within colon cancers removed by resection and 16 tissue samples were taken near tubulovillous adenomas (TVAs) removed by resection. 568 triplicate tissue sections (a total of 1,704 tissue sections) from these tissue samples were evaluated by immunohistochemistry for 4 DNA repair proteins. Substantially reduced protein expression of Pms2, Ercc1 and Xpf occurred in field defects of up to 10 cm longitudinally distant from colon cancers or TVAs and within colon cancers. Expression of another DNA repair protein, Ku86, was infrequently reduced in these areas. When Pms2, Ercc1 or Xpf were reduced in protein expression, then either one or both of the other two proteins most often had reduced protein expression as well. The mean inner colon circumferences, from 32 resections, of the ascending, transverse and descending/sigmoid areas were measured as 6.6 cm, 5.8 cm and 6.3 cm, respectively. When combined with other measurements in the literature, this indicates the approximate mean number of colonic crypts in humans is 10 million.

Conclusions

The substantial deficiencies in protein expression of DNA repair proteins Pms2, Ercc1 and Xpf in about 1 million crypts near cancers and TVAs suggests that the tumors arose in field defects that were deficient in DNA repair and that deficiencies in Pms2, Ercc1 and Xpf are early steps, often occurring together, in progression to colon cancer.