bluuebunny/crossref_metadata_2025 huggingface dataset:
Experiencing Breast Cancer in Managed Care
Authors: Wenzel Jennifer , Steeves Richard H.
Published: October 2008

The interest of managed care organizations (MCOs) in decreasing care and outcome variance and lowering costs has created many concerns including those pertaining to the complex and costly nature of cancer care. In this study, we used a hermeneutic phenomenological approach involving semistructured interviews of 14 women with breast cancer to examine MCO enrollees' experiences related to their cancer treatment. Results comprise two themes: managed care tasks and managing or mediating between the MCO and the cancer. These themes, and their accompanying categories, depict the increased burden encountered by women experiencing breast cancer in a managed care system who perceived that they were solely responsible for mediating between their care providers and MCO. Though enrolled in less-restrictive MCOs, participants expressed many difficulties in managing dissimilar and disconnected demands posed by the cancer and the MCO. These findings might serve as a basis for policy and practice changes to decrease this real patient burden.
Parental Perceptions of Overweight During Early Childhood
Authors: Suzanne Goodell L. , Pierce Michelle B. , Bravo Carolina M. , Ferris Ann M.
Published: October 2008

Prior to developing an overweight prevention program, researchers examined perceptions of overweight during early childhood among minority, low-socioeconomic status (SES) parents of preschoolers living in Hartford, Connecticut (USA). Content analysis of 10 focus groups (average size = 7) and 18 follow-up interviews revealed parents have a distorted, detached view of clinically defined overweight preschoolers, and they do not include weight in their definition of health. The result is a disconnect in communicating with health care providers regarding overweight during early childhood. Findings suggest that overweight intervention programs will be more effective by focusing on the main concern of parents, which is good health rather than weight. By developing new approaches to communicating the diagnosis and implications of overweight during early childhood, health providers are more likely to be able to work collaboratively with parents to prevent and treat overweight during early childhood.
Variables Influencing Physiotherapy Adherence Among Young Adults With Cerebral Palsy
Authors: Redmond Rebecca , Parrish Margarete
Published: October 2008

The findings of this qualitative study provide insight into a range of developmental and personal variables that influence whether young adults with cerebral palsy adhere to physiotherapy programs and advice from physiotherapists, with the aim of improving the quality of services offered to such a population. The study participants included young adults with cerebral palsy between the ages of 16 and 25 years who were enrolled in a college devoted to training disabled young adults. They attended focus groups to discuss their experiences of physiotherapy. A constant comparative method was used within the grounded theory approach for the collection and analysis of data. The results demonstrate that the interaction between physiotherapist and young adult is the essential variable, with the relationship formed being built with trust, respect, and empowerment of the participant. This study offered a valuable opportunity for those often considered too vulnerable to participate in research.
A Fine Line to Walk: Case Managers' Perspectives on Sharing Information With Families
Authors: Chen Fang-pei
Published: October 2008

In the United States, sharing information with families in health care involves competing demands between clients' rights to confidentiality and families' wishes to know. In this article, I explore how community mental health providers share information with families of clients with severe mental illness. I interviewed 24 case managers in assertive community treatment programs. Results show that case managers share information with families to attain treatment goals rather than to support families in providing care. Case managers respect clients' confidentiality and do not release information without client consent. However, the absence of client consent posts an ethical dilemma when families provide helpful information for clients' treatment. Case managers find themselves walking a fine line between adhering to confidentiality guidelines and working for the clients' best interests. The findings suggest the need to expand confidentiality laws to the exchange of information and to develop guidelines for working with families in community settings.
“I'm not a saint”: Burden Assessment as an Unrecognized Factor in Prenatal Decision Making
Authors: McCoyd Judith L. M.
Published: October 2008

Prenatal testing is widely utilized, yet few studies have explored decision-making processes about diagnosis from the pregnant woman's standpoint. This qualitative, exploratory study reveals a factor not accounted for in prior research geared toward associations between demographic categories and decisions. The 30 women in this study demonstrated a three-part decisional trajectory that included an effort to collect information about the challenges a potential child with their particular diagnosis might experience. They then assessed their social context, familial supports, and resilience as a couple. A final yet crucial step was an assessment of the woman's own capacity to provide this level of care within her unique context. Few genetics teams have a member with biopsychosocial expertise and time who can help the woman/couple reflect on the situated context of the decision and its impact. Better care strategies to support women and couples through this experience are warranted.
Maintaining Integrity: Women and Treatment Seeking for the Symptoms of Potential Cardiac Illness
Authors: Turris Sheila A. , Johnson Joy L.
Published: October 2008

Cardiac disease is the number one killer of Canadian women. Therapy is highly time-dependent, yet treatment-seeking delay persists. The purpose of this grounded theory study was to explore how women seeking treatment for the symptoms of potential cardiac illness interpreted their symptoms, made decisions about seeking treatment, and understood experiences of care in the emergency department. Data were drawn from 100 hours of naturalistic observation, in-depth interviews with 16 women who visited one of two urban emergency departments between June 2005 and June 2006, and three interviews with nurses. The basic social psychological process of maintaining integrity was identified, encompassing three distinct phases: “resisting disruption,” “suspending agency,” and “integrating experiences and knowledge.” The findings suggest that in the face of a threat to life, women are first and foremost striving to maintain both the integrity of their sense of self and their ability to carry out role responsibilities.
Contradictions and Misperceptions: An Exploration of Injecting Practice, Cleanliness, Risk, and Partnership in the Lives of Women Drug Users
Authors: Sheard Laura , Tompkins Charlotte
Published: October 2008

We report the findings of an in-depth interview study conducted with 45 women injecting drug users in Britain. Women described experiences of injecting themselves and being injected by others, including instances of bodily harm and pain. Cleanliness when injecting was an issue of particular importance. An interesting division (“line of decency”) occurred between opinions on sharing needles versus sharing injecting equipment. Partnership dynamics were important and partners sometimes had a pervasive influence on women's drug use and injecting practices. Narratives of risk showed that some women understood the risk of blood-borne viruses and outlined practical risk-prevention strategies. Some women did not perceive themselves to be at particular risk. Moral opinions were voiced about the risk behavior of others. Notions of risk were highly contextual and depended on a woman's immediate injecting situation. This article reports the inherent complexity resident in women drug users' decisions surrounding their injecting behavior.
Incumbent and Challenger Campaign Spending Effects in Proportional Electoral Systems
Authors: Benoit Kenneth , Marsh Michael
Published: October 2008

Positive effects of campaign spending on electoral outcomes have been found in several comparative, multiparty contexts, but very few of these systems use proportional representation. The few studies examining spending effects in multiparty elections have found that incumbent spending is no less effective than challenger spending, contrary to the vast bulk of empirical literature drawn from single-member district contexts. This study reexamines incumbent—challenger differences in spending effects under the single transferable vote. Examining the Irish general elections of 2002, the authors find a positive and statistically significant relationship between spending and votes. Candidates that spend more win more votes, and outspending one’s rivals means winning more of the vote share. Spending more also directly increases a candidate’s chance of winning a seat. Finally, incumbent spending is considerably less effective than spending by challengers from other parties but no less effective than spending by challengers from a candidate’s own party.
Intimate Partner Violence and Women's Contraceptive Use
Authors: Williams Corrine M. , Larsen Ulla , McCloskey Laura A.
Published: October 2008

Intimate partner violence has been hypothesized as a factor associated with women's risk for problems in contraception use or access. This article explores differences in contraceptive use between abused and nonabused women, using a case—control study of 225 women. Women experiencing physical and emotional abuse were more likely to report not using their preferred method of contraception in the past 12 months compared with nonabused women (OR = 1.9; 95% CI = 1.0 to 3.7). Health care providers need to consider how intimate partner violence may influence their patients' use of contraceptives, which has implications for the high risk of unintended pregnancies among abused women.
Patient education program to enhance decision autonomy in multiple sclerosis relapse management: a randomized-controlled trial
Authors: Köpke S , Kasper J , Mühlhauser I , Nübling M , Heesen C
Published: October 2008

Background

Contrary to strong recommendations for high-dose intravenous corticosteroid treatment for relapses in multiple sclerosis (MS), uncertainty remains about most aspects of relapse management. Oral corticosteroids administered by physicians or patients themselves or no corticosteroids also appear justifiable.

Objective

To evaluate an education program that aims to involve patients with MS in decisions on relapse management.

Methods

In three German MS centers, 150 patients with relapsing MS were randomly assigned to a single, 4-h group session or a standard information leaflet. The primary outcome measure was the proportion of relapses with oral or no corticosteroid therapy as an indicator of patient autonomy in treatment decision making. Other outcomes included perceived decision autonomy, quality of life, and disability status.

Results

In the intervention group (IG), 108/139 (78%) relapses were treated with oral or no corticosteroids compared with 101/179 (56%) in the control group; P < 0.0001. Patients’ perceived autonomy of treatment decision making was significantly higher in the IG; P < 0.0001. Quality of life, disability status, and adverse events of corticosteroid therapies were comparable.

Conclusion

The patient education program led to more autonomous decision making in patients with relapsing MS. Relevant changes in relapse management were observed.
High frequency of adverse health behaviors in multiple sclerosis
Authors: Marrie RA , Horwitz R , Cutter G , Tyry T , Campagnolo D , Vollmer T
Published: October 2008

Background

Health behaviors influence chronic disease risks in the general population, and may influence health outcomes independently of comorbid diseases. Health behaviors receive less attention in multiple sclerosis (MS) than in the general population. We assessed health behaviors among participants in the North American Research Committee on Multiple Sclerosis (NARCOMS) Registry and the demographic characteristics associated with particular health behaviors.

Methods

In October 2006, we surveyed NARCOMS participants regarding smoking using questions from the Behavioral Risk Factor Surveillance Survey; physical activity using questions from the PEPI study, alcohol use using the AUDIT-C; and height and weight. To determine the independent demographic predictors of health behaviors, we used multivariable logistic regression, either binary or polytomous as appropriate.

Results

Of 8983 responders, 4867 (54.2%) ever smoked; 1542 (17.3%) currently smoked. On the basis of the AUDIT-C, 1632 (18.2%) were at risk for alcohol abuse or dependence. A quarter of participants were obese ( n = 2269), and 2780 (31.3%) were overweight. Fewer than 25% of participants reported moderate or heavy leisure-time physical activity. Generally, lower socioeconomic status was associated with a higher frequency of adverse health behaviors accounting for other demographic factors. With increasing levels of disability, the reported intensity of physical activity was lower, and the frequency of overweight or obesity was higher.

Conclusions

Patients with MS exhibit frequent adverse health behaviors, increasing the risk of other chronic diseases. Further research is needed to determine how these behaviors influence disability progression, quality of life, and other MS-related outcomes.
The distribution of new enhancing lesion counts in multiple sclerosis: further explorations
Authors: van den Elskamp IJ , Knol DL , Uitdehaag BMJ , Barkhof F
Published: October 2008

Background

A statistical distribution describing the number of new enhancing lesions seen on MRI in patients with MS is of great importance for improving the statistical methodology of clinical trials using new enhancing lesions as outcome measure. We examined whether there are superior alternatives for the currently proposed negative binomial (NB) distribution.

Objective

To determine the optimal statistical distribution describing new enhancing lesion counts from a selection of six conceivable models, and to assess the effect on the distribution of a treatment effect, varying follow-up duration and selection for activity at baseline.

Methods

The statistical NB, Poisson-Inverse Gaussian (P-IG), Poisson- Lognormal (P-LN), Neyman type A (NtA), Pólya-Aeppli (PA) and Zero Inflated Poisson (ZIP) distribution were fitted on new enhancing lesion data derived from one treated and two untreated cohorts of RRMS and relapsing SPMS patients and on subgroups of varying follow-up duration and selection for baseline activity. Measure of comparison was Akaike's information criterion (AIC).

Results

Both the subgroup analyses as well as a treatment had a noticeable effect on the distributional characteristics of new enhancing lesion counts. The NB distribution generally provided the most optimal fit, closely followed by the P-IG distribution and the P-LN distribution. Fits of the PA and NtA distribution were suboptimal, while the ZIP distribution was the least adequate for modelling new enhancing lesion counts.

Conclusion

The NB distribution is the optimal distribution for modelling new enhancing lesion counts, irrespective of the effect of treatment, follow-up duration or a baseline activity selection criterion.
Sensory impairments in quiet standing in subjects with multiple sclerosis
Authors: Cattaneo D , Jonsdottir J
Published: October 2008

Balance disorders and falls are frequently observed in subjects with multiple sclerosis (MS). Along with motor impairment, sensory disorders and integration deficits of sensory inputs lead to inadequate motor responses. The assessment of these sensory disorders in an every day tasks, such as upright stance, increases our knowledge of postural control in this pathology, thus promoting more effective treatments. The aim of the study was to describe sensory impairments and sensory strategies in different sensory conditions. A stabilometric assessment was carried out in a consecutive convenience sample of 53 subjects. The age of the sample was 52.7 (21.1) years; the onset of pathology was 27.20 (14.5) years before the assessment. Balance was assessed in six sensory conditions. The impact of pathology on balance control was shown by the high percentage of abnormal scores: 75% of subjects with MS showed abnormal scores even in the eyes open condition. The alteration of a single sensory input led to an increase of abnormal scores in up to 82% of subjects. Almost all subjects showed abnormal scores in the vestibular conditions where 22% of them fell. The pattern of the subjects’ performance in the six sensory conditions suggests that balance control may be more correlated to the number of reliable sensory inputs than the nature of the sensory input itself.
Spinal cord grey matter lesions in multiple sclerosis detected by post-mortem high field MR imaging
Authors: Gilmore CP , Geurts JJG , Evangelou N , Bot JCJ , van Schijndel RA , Pouwels PJW , Barkhof F , Bö L
Published: October 2008

Background

Post-mortem studies demonstrate extensive grey matter demyelination in MS, both in the brain and in the spinal cord. However the clinical significance of these plaques is unclear, largely because they are grossly underestimated by MR imaging at conventional field strengths. Indeed post-mortem MR studies suggest the great majority of lesions in the cerebral cortex go undetected, even when performed at high field. Similar studies have not been performed using post-mortem spinal cord material.

Aim

To assess the sensitivity of high field post-mortem MRI for detecting grey matter lesions in the spinal cord in MS.

Methods

Autopsy material was obtained from 11 MS cases and 2 controls. Proton Density-weighted images of this formalin-fixed material were acquired at 4.7Tesla before the tissue was sectioned and stained for Myelin Basic Protein. Both the tissue sections and the MR images were scored for grey matter and white matter plaques, with the readers of the MR images being blinded to the histopathology results.

Results

Our results indicate that post-mortem imaging at 4.7Tesla is highly sensitive for cord lesions, detecting 87% of white matter lesions and 73% of grey matter lesions. The MR changes were highly specific for demyelination, with all lesions scored on MRI corresponding to areas of demyelination.

Conclusion

Our work suggests that spinal cord grey matter lesions may be detected on MRI more readily than GM lesions in the brain, making the cord a promising site to study the functional consequences of grey matter demyelination in MS.
Quantitative PCR for Epstein–Barr virus DNA and RNA in multiple sclerosis
Authors: Lindsey JW , Hatfield LM , Crawford MP , Patel S
Published: October 2008

Background

Epstein–Barr virus (EBV) is associated with MS, but it is not clear whether EBV plays a role in the pathogenesis of MS.

Hypothesis

We hypothesized that the immune control of EBV might be defective in MS, and that reactivation of EBV might drive the immune response in MS.

Methods

We collected blood from controls and patients with MS, and measured the amounts of EBV DNA and RNA using quantitative PCR.

Results

We found that EBV DNA and RNA were frequently detectable in peripheral blood leukocytes from both patients with MS and normal controls. There was no significant difference between patients with MS or controls. Paired samples from a small number of subjects suggest that EBV DNA may increase before and during clinical relapse.

Conclusions

We conclude that the immune control of EBV infection is similar in MS and controls, and that reactivation of EBV may correlate with MS disease activity.
Validation of the Multiple Sclerosis Neuropsychological Screening Questionnaire in Argentina
Authors: Vanotti S , Benedict RHB , Acion L , Cáceres F ,   and VANEM Workgroup
Published: October 2008

Backgrounds

Considering the lack of screening technology that would permit neurologists to identify patients who may benefit from formal or more comprehensive assessment of neuropsychological status in patients with multiple sclerosis (MS) in Argentina, we felt the need to validate the Multiple Sclerosis Neuropsychological Screening Questionnaire (MSNQ) developed by Benedict, et al.

Objective

The objective in this multicenter study was to test the reliability and validity of the MSNQ after translation into Spanish in Argentina. We also compared the MSNQ yield by the patient report with that of the two different informants. The sample included 125 patients with MS and 36 normal controls, 27 patients had two informants available and 23 patients and their informants were examined twice at 1-week intervals (test–retest group). All participants completed the MSNQ, RAO BRB, Beck Depression Inventory-Fast Screen, EDSS, and MS Functional Composite.

Results

We found that an MSNQ-I score of 26 or more resulted in classifications yielding sensitivity of 0.91 and specificity of 0.80, suggesting some utility for this Argentine, informant-report measure.

Conclusions

This Spanish version of the MSNQ is reliable and useful as a screening test for identifying patients at high risk for cognitive impairment in MS.
Democracy and Political Parties
Authors: Rahat Gideon , Hazan Reuven Y. , Katz Richard S.
Published: October 2008

If the quality of democracy incorporates values beyond simple majority choice, then is intra-party democracy likely to further or to impede the advancement of these other values? We address the relationship between internal party democracy, as indicated by the inclusiveness of parties' selectorates, and the realization of two associated democratic values — the extent of both competition in the nomination process and representation among the lists of candidates that emerge. Although we analyse these relationships within party, our interest in them is primarily for their system level impact. We find that the three democratic values of inclusive participation, competition and representativeness are unlikely to be simultaneously maximized. Rather, the relationships among these values may be non-linear, or even negative. In particular, the parties that are most internally democratic produce lists of candidates that are least representative and experience only medium levels of competition.
A Decade Later, the World Had Changed, the Cleavage Structure Remained
Authors: Arian Asher , Shamir Michal
Published: October 2008

The defining challenge for Israel since 1967 has been the future of the territories captured in the Six Day War and the population living in them. With the stalemate festering and the salience of the conflict very high, the conflict with the Palestinians has become the major cleavage dimension in Israeli politics. Building on the multidimensional conceptualization of cleavage, we argue that despite the occurrence of many, dramatic, changes, the cleavage structure has not changed in the past decade, and the 1977 realignment is still in place. The primary cleavage is a full and consistent interlocking cleavage. Its potency, and the quality that permits it to achieve this overarching position, is associated with its expression of underlying collective identity dilemmas, which combine external and internal dimensions. Collective identity concerns, more readily than others, produce full cleavages and are likely to dominate and endure, overriding other issues. The establishment, positioning and success of Kadima in the 2006 elections are explicated within this framework.
Unaccounted Competition
Authors: Hofnung Menachem
Published: October 2008

In most countries, national, inter-party elections are financed and regulated by national authorities, while there is little interference or supervision of intra-party elections. This is especially true in countries with proportional representation or mixed electoral systems. In this article I question the wisdom of ignoring the regulation of intra-party elections and examine the pitfalls created by regulating only one part of the democratic electoral process, i.e. national elections, while leaving the preliminary cycle of leadership and candidate selection, which takes place largely within the parties, open to free, uncontrolled and unsupervised competition.
Fighting Terrorism in the Political Arena
Authors: Navot Suzie
Published: October 2008

In recent years, Western democracies have attempted to outlaw political parties alleged to be `non-democratic'. Provisions in post-World War II constitutions were mainly enacted to exclude Nazi and Fascist parties from participating in the elections. Lately, the banning of political parties has spread to radical and religious parties. Recent debates in Spain, Germany, Turkey and Israel provide some examples of this. This article deals with the legal framework for the disqualification of political parties in Israel, focusing on the new anti-terrorist amendment, which allows for banning lists and individual candidates who support terrorist acts and the use of violence. The new grounds for banning parties are also discussed in a comparative perspective, vis-à-vis the new Spanish law of 2002. The article reveals the dilemmas of Israel, a `defensive' democracy, in its attempt to deal with support for terrorism by outlawing political parties.
Assessing Presidential Power
Authors: Kelley Christopher S. , Marshall Bryan W.
Published: October 2008

Presidents have a wide array of strategies to influence legislation. One area that has seen less emphasis in the literature is the executive's unilateral ability to issue signing statements and their role in shaping policy. We develop a spatial model illustrating how the president's bargaining power with Congress can be expanded when the veto threat is coordinated with signing statements. The analysis suggests that signing statements, although underappreciated, may potentially be a valuable presidential tool in the veto bargaining process. The analysis also shows that veto threats are a key factor explaining the president's use of the constitutional signing statement. We infer that veto threats and signing statements are linked together as part of a larger coordinated strategy to exert presidential power in the legislative realm.
Galantamine for the Treatment of BPSD in Thai Patients With Possible Alzheimer's Disease With or Without Cerebrovascular Disease
Authors: Tangwongchai S. , Thavichachart N. , Senanarong V. , Poungvarin N. , Phanthumchinda K. , Praditsuwan R. , Nidhinandana S. , Chankrachang S.
Published: October 2008

Objectives. This study was to investigate an efficacy of galantamine in treatment of behavioral and psychological symptoms of dementia in Thai elderly who suffered from possible Alzheimer's disease (AD) with or without cerebrovascular disease and vascular dementia.

Methods. A 6-month, multicenter, open-label, uncontrolled trial was undertaken in 75 patients. Eligible patients received an initial galantamine dose of 8 mg/dayand escalated over 5 to 8 weeks to maintenance doses of 16 or 24 mg/day. The behavioral response was assessed as an intention-to-treat analysis using the Behavioral Pathology in Alzheimer's Disease Rating Scale (BEHAVE-AD).

Results. Galantamine improved behavioral and psychological symptoms of dementia ( P < .05 vs baseline) over the 24 weeks of treatment. BEHAVE-AD score was significantly improved from baseline in paranoid and delusion ideation, diurnal rhythm disturbances, anxieties, and phobias.

Conclusions. Galantamine may be a well-tolerated and effective treatment option for improving psychotic, behavioral, and psychological symptoms in Thai elderly with possible AD with or without cerebrovascular disease and vascular dementia.
Ultrasonic induced structural modification in Mg alloys
Authors: Shepelev D. , Oshri G. , Graznov P. , Goren-Muginstein G. , Moldavsky L. , Shuster K. , Fichman M. , Bamberger M.
Published: October 2008

Ultrasonic waves (frequency 20 kHz and maximum intensity 400 W) were applied in molten Mg alloys during solidification to a cylinder 30 mm in diameter and 100 mm long. Applying this treatment to Mg–4Zn–4Sn–1Si resulted in refinement of the dendritic structure and more uniform dispersion of the Mg2Sn and Mg2Si precipitates. The same treatment carried out on Mg–1·5Ca–3Zn alloy resulted in transition from dendritic solidification to equiaxed structure with a relatively uniform grain size. In addition, the formation of Mg2Ca was significantly suppressed.
Anglo-Danish Library Connections in the Post-War Era: An Illustration of Cultural Aspects of the Transition from Warfare to Welfare Societies in the Years 1945 to 1964
Authors: Dyrbye Martin
Published: October 2008

Examines connections between the public library movements in Britain and Denmark in the twenty-year period following the Second World War. Focuses on the cultural dimensions of these connections, in terms of both the library and non-library worlds. The long-standing annexation of the Anglo-American library model was matched in the 1950s and 1960s by British admiration for public library developments in Denmark. In matters ranging from public library purpose, library legislation and funding and service standardization, to outreach and extension work, the development of rural and mobile provision and the selection of new media and popular literature, both the exchange of information and face-to-face discussions among librarians from the two countries were of great importance.
Booksellers as Publishers in Estonia in the Second Half of the Nineteenth Century and at the Beginning of the Twentieth Century
Authors: Jantson Signe
Published: October 2008

The article handles general developments and changes in book trade and publishing which took place in Estonia during the second half of the nineteenth century and the beginning of the twentieth century. The aim is to show the publishing activities of Estonian booksellers and to analyse the activities of Estonian booksellers and development of book production (printing) and publishing of Estonian language books. The survey is based on the research literature and on the master thesis by Signe Jantson, Book Trade in Estonia 1850–1917: Bookshops and their Owners. Up to the middle of the nineteenth century the book production and dissemination in Estonia was in the hands of Baltic German entrepreneurs and depended on the political and economic developments not only in Russia but also in Germany. The Estonian national awakening movement was preceded by the birth of Estonian national literature in the middle of the nineteenth century. In the period of the next fifty years the publication of Estonian language books increased tenfold. The second half of the nineteenth century and the beginning of the twentieth century was still favourable for the book trade: 263 new shops were opened and 283 new persons tried to start book trade businesses, but trading with books did not guarantee sufficient income and the bookshop owners were often engaged in other spheres. Among the 283 bookshop owners, 83 headed companies comprising the publishing house, the printing office, and the bookshop.
Functional Epstein-Barr virus reservoir in plasma cells derived from infected peripheral blood memory B cells
Authors: Al Tabaa Yassine , Tuaillon Edouard , Bollore Karine , Foulongne Vincent , Petitjean Gael , Seigneurin Jean-Marie , Duperray Christophe , Desgranges Claude , Vendrell Jean-Pierre
Published: October 2008

The Epstein-Barr virus (EBV) causes infectious mononucleosis, establishes latency in resting memory B lymphocytes, and is involved in oncogenesis through poorly understood mechanisms. The EBV lytic cycle is initiated during plasma cell differentiation by mRNAs transcripts encoded by BZLF1, which induce the synthesis of EBV proteins such as the immediate-early antigen ZEBRA and the late membrane antigen gp350. Therefore, we assessed the capacity of circulating EBV-infected B lymphocytes from healthy EBV-seropositive subjects to enter and complete the EBV lytic cycle. Purified B lymphocytes were polyclonally stimulated and BZLF1- or gp350-secreting cells (BZLF1-SCs or gp350-SCs) were enumerated by ELISpot assays. The number of BZLF1-SCs ranged from 50 to 480/107 lymphocytes (median, 80; 25th-75th percentiles, 70-150) and gp350-SCs from 10 to 40/107 lymphocytes (median, 17; 25th-75th percentiles, 10-20). gp350-SCs represented only 7.7% to 28.6% of BZLF1-SCs (median, 15%; 25th-75th percentiles, 10.5%-20%). This EBV functional reservoir was preferentially restricted to plasma cells derived from CD27+ IgD− memory B lymphocytes. In 9 of 13 subjects, EBV DNA quantification in B-cell culture supernatants gave evidence of completion of EBV lytic cycle. These results demonstrate that EBV proteins can be secreted by EBV-infected B lymphocytes from healthy carriers, a majority generating an abortive EBV lytic cycle and a minority completing the cycle.
Granulocyte/macrophage–colony-stimulating factor autoantibodies and myeloid cell immune functions in healthy subjects
Authors: Uchida Kanji , Nakata Koh , Suzuki Takuji , Luisetti Maurizio , Watanabe Masato , Koch Diana E. , Stevens Carrie A. , Beck David C. , Denson Lee A. , Carey Brenna C. , Keicho Naoto , Krischer Jeffrey P. , Yamada Yoshitsugu , Trapnell Bruce C.
Published: October 2008

High levels of granulocyte/macrophage–colony-stimulating factor (GM-CSF) autoantibodies are thought to cause pulmonary alveolar proteinosis (PAP), a rare syndrome characterized by myeloid dysfunction resulting in pulmonary surfactant accumulation and respiratory failure. Paradoxically, GM-CSF autoantibodies have been reported to occur rarely in healthy people and routinely in pharmaceutical intravenous immunoglobulin (IVIG) purified from serum pooled from healthy subjects. These findings suggest that either GM-CSF autoantibodies are normally present in healthy people at low levels that are difficult to detect or that serum pooled for IVIG purification may include asymptomatic persons with high levels of GM-CSF autoantibodies. Using several experimental approaches, GM-CSF autoantibodies were detected in all healthy subjects evaluated (n = 72) at low levels sufficient to rheostatically regulate multiple myeloid functions. Serum GM-CSF was more abundant than previously reported, but more than 99% was bound and neutralized by GM-CSF autoantibody. The critical threshold of GM-CSF autoantibodies associated with the development of PAP was determined. Results demonstrate that free serum GM-CSF is tightly maintained at low levels, identify a novel potential mechanism of innate immune regulation, help define the therapeutic window for potential clinical use of GM-CSF autoantibodies to treat inflammatory and autoimmune diseases, and have implications for the pathogenesis of PAP.
The enzymatic activity of 5-aminoimidazole-4-carboxamide ribonucleotide formyltransferase/IMP cyclohydrolase is enhanced by NPM-ALK: new insights in ALK-mediated pathogenesis and the treatment of ALCL
Authors: Boccalatte Francesco E. , Voena Claudia , Riganti Chiara , Bosia Amalia , D'Amico Lucia , Riera Ludovica , Cheng Mangeng , Ruggeri Bruce , Jensen Ole N. , Goss Valerie L. , Lee Kimberly , Nardone Julie , Rush John , Polakiewicz Roberto D. , Comb Michael J. , Chiarle Roberto , Inghirami Giorgio
Published: October 2008

Anaplastic large cell lymphoma represents a subset of neoplasms caused by translocations that juxtapose the anaplastic lymphoma kinase (ALK) to dimerization partners. The constitutive activation of ALK fusion proteins leads to cellular transformation through a complex signaling network. To elucidate the ALK pathways sustaining lymphomagenesis and tumor maintenance, we analyzed the tyrosine-kinase protein profiles of ALK-positive cell lines using 2 complementary proteomic-based approaches, taking advantage of a specific ALK RNA interference (RNAi) or cell-permeable inhibitors. A well-defined set of ALK-associated tyrosine phosphopeptides, including metabolic enzymes, kinases, ribosomal and cytoskeletal proteins, was identified. Validation studies confirmed that vasodilator-stimulated phosphoprotein and 5-aminoimidazole-4-carboxamide ribonucleotide formyltransferase/inosine monophosphate cyclohydrolase (ATIC) associated with nucleophosmin (NPM)–ALK, and their phosphorylation required ALK activity. ATIC phosphorylation was documented in cell lines and primary tumors carrying ALK proteins and other tyrosine kinases, including TPR-Met and wild type c-Met. Functional analyses revealed that ALK-mediated ATIC phosphorylation enhanced its enzymatic activity, dampening the methotrexate-mediated transformylase activity inhibition. These findings demonstrate that proteomic approaches in well-controlled experimental settings allow the definition of informative proteomic profiles and the discovery of novel ALK downstream players that contribute to the maintenance of the neoplastic phenotype. Prediction of tumor responses to methotrexate may justify specific molecular-based chemotherapy.
Mutation of the β1-tubulin gene associated with congenital macrothrombocytopenia affecting microtubule assembly
Authors: Kunishima Shinji , Kobayashi Ryoji , Itoh Tomohiko J. , Hamaguchi Motohiro , Saito Hidehiko
Published: October 2008

Congenital macrothrombocytopenia is a genetically heterogeneous group of rare disorders. We identified the first TUBB1 mutation, R318W, in a patient with congenital macrothrombocytopenia. The patient was heterozygous for Q43P, but this single-nucleotide polymorphism (SNP) did not relate to macrothrombocytopenia. Although no abnormal platelet β1-tubulin localization/marginal band organization was observed, the level of β1-tubulin was decreased by approximately 50% compared with healthy controls. Large and irregular bleb protrusions observed in megakaryocytes derived from the patient's peripheral blood CD34+ cells suggested impaired megakaryocyte fragmentation and release of large platelets. In vitro transfection experiments in Chinese hamster ovary (CHO) cells demonstrated no incorporation of mutant β1-tubulin into microtubules, but the formation of punctuated insoluble aggregates. These results suggested that mutant protein is prone to aggregation but is unstable within megakaryocytes/platelets. Alternatively, mutant β1-tubulin may not be transported from the megakaryocytes into platelets. W318 β1-tubulin may interfere with normal platelet production, resulting in macrothrombocytopenia.
Protein phosphatase 2A inactivates Bcl2's antiapoptotic function by dephosphorylation and up-regulation of Bcl2-p53 binding
Authors: Deng Xingming , Gao Fengqin , May W. Stratford
Published: October 2008

Bcl2 is associated with chemoresistance and poor prognosis in patients with various hematologic malignancies. DNA damage-induced p53/Bcl2 interaction at the outer mitochondrial membrane results in a Bcl2 conformational change with loss of its antiapoptotic activity in interleukin-3–dependent myeloid H7 cells. Here we find that specific disruption of protein phosphatase 2A (PP2A) activity by either expression of small t antigen or depletion of PP2A/C by RNA interference enhances Bcl2 phosphorylation and suppresses cisplatin-stimulated p53/Bcl2 binding in association with prolonged cell survival. By contrast, treatment of cells with C2-ceramide (a potent PP2A activator) or expression of the PP2A catalytic subunit (PP2A/C) inhibits Bcl2 phosphorylation, leading to increased p53/Bcl2 binding and apoptotic cell death. Mechanistically, PP2A-mediated dephosphorylation of Bcl2 in vitro promotes its direct interaction with p53 as well as a conformational change in Bcl2. PP2A directly interacts with the BH4 domain of Bcl2 as a docking site to potentially “bridge” PP2A to Bcl2's flexible loop domain containing the target serine 70 phosphorylation site. Thus, PP2A may provide a dual inhibitory effect on Bcl2's survival function by both dephosphorylating Bcl2 and enhancing p53-Bcl2 binding. Activating PP2A to dephosphorylate Bcl2 and/or increase Bcl2/p53 binding may represent an efficient and novel approach for treatment of hematologic malignancies.
Unique genes in plants: specificities and conserved features throughout evolution
Authors: Armisén David , Lecharny Alain , Aubourg Sébastien
Published: October 2008

Background

Plant genomes contain a high proportion of duplicated genes as a result of numerous whole, segmental and local duplications. These duplications lead up to the formation of gene families, which are the usual material for many evolutionary studies. However, all characterized genomes include single-copy (unique) genes that have not received much attention. Unlike gene duplication, gene loss is not an unspecific mechanism but is rather influenced by a functional selection. In this context, we have established and used stringent criteria in order to identify suitable sets of unique genes present in plant proteomes. Comparisons of unique genes in the green phylum were used to characterize the gene and protein features exhibited by both conserved and species-specific unique genes.

Results

We identified the unique genes within both A. thaliana and O. sativa genomes and classified them according to the number of homologs in the alternative species: none (U{1:0}), one (U{1:1}) or several (U{1:m}). Regardless of the species, all the genes in these groups present some conserved characteristics, such as small average protein size and abnormal intron number. In order to understand the origin and function of unique genes, we further characterized the U{1:1} gene pairs. The possible involvement of sequence convergence in the creation of U{1:1} pairs was discarded due to the frequent conservation of intron positions. Furthermore, an orthology relationship between the two members of each U{1:1} pair was strongly supported by a high conservation in the protein sizes and transcription levels. Within the promoter of the unique conserved genes, we found a number of TATA and TELO boxes that specifically differed from their mean number in the whole genome. Many unique genes have been conserved as unique through evolution from the green alga Ostreococcus lucimarinus to higher plants. Plant unique genes may also have homologs in bacteria and we showed a link between the targeting towards plastids of proteins encoded by plant nuclear unique genes and their homology with a bacterial protein.

Conclusion

Many of the A. thaliana and O. sativa unique genes are conserved in plants for which the ancestor diverged at least 725 million years ago (MYA). Half of these genes are also present in other eukaryotic and/or prokaryotic species. Thus, our results indicate that (i) a strong negative selection pressure has conserved a number of genes as unique in genomes throughout evolution, (ii) most unique genes are subjected to a low divergence rate, (iii) they have some features observed in housekeeping genes but for most of them there is no functional annotation and (iv) they may have an ancient origin involving a possible gene transfer from ancestral chloroplasts or bacteria to the plant nucleus.
Toxicogenomic response of Pseudomonas aeruginosa to ortho-phenylphenol
Authors: Nde Chantal W , Jang Hyeung-Jin , Toghrol Freshteh , Bentley William E
Published: October 2008

Background

Pseudomonas aeruginosa (P. aeruginosa) is the most common opportunistic pathogen implicated in nosocomial infections and in chronic lung infections in cystic fibrosis patients. Ortho-phenylphenol (OPP) is an antimicrobial agent used as an active ingredient in several EPA registered disinfectants. Despite its widespread use, there is a paucity of information on its target molecular pathways and the cellular responses that it elucidates in bacteria in general and in P. aeruginosa in particular. An understanding of the OPP-driven gene regulation and cellular response it elicits will facilitate more effective utilization of this antimicrobial and possibly lead to the development of more effective disinfectant treatments.

Results

Herein, we performed a genome-wide transcriptome analysis of the cellular responses of P. aeruginosa exposed to 0.82 mM OPP for 20 and 60 minutes. Our data indicated that OPP upregulated the transcription of genes encoding ribosomal, virulence and membrane transport proteins after both treatment times. After 20 minutes of exposure to 0.82 mM OPP, genes involved in the exhibition of swarming motility and anaerobic respiration were upregulated. After 60 minutes of OPP treatment, the transcription of genes involved in amino acid and lipopolysaccharide biosynthesis were upregulated. Further, the transcription of the ribosome modulation factor (rmf) and an alternative sigma factor (rpo S) of RNA polymerase were downregulated after both treatment times.

Conclusion

Results from this study indicate that after 20 minutes of exposure to OPP, genes that have been linked to the exhibition of anaerobic respiration and swarming motility were upregulated. This study also suggests that the downregulation of the rmf and rpoS genes may be indicative of the mechanism by which OPP causes decreases in cell viability in P. aeruginosa. Consequently, a protective response involving the upregulation of translation leading to the increased synthesis of membrane related proteins and virulence proteins is possibly induced after both treatment times. In addition, cell wall modification may occur due to the increased synthesis of lipopolysaccharide after 60 minutes exposure to OPP. This gene expression profile can now be utilized for a better understanding of the target cellular pathways of OPP in P. aeruginosa and how this organism develops resistance to OPP.
Differential gene expression profiles are dependent upon method of peripheral blood collection and RNA isolation
Authors: Asare Adam L , Kolchinsky Svetlana A , Gao Zhong , Wang Richard , Raddassi Khadir , Bourcier Katarzyna , Seyfert-Margolis Vicki
Published: October 2008

Background

RNA isolation and purification steps greatly influence the results of gene expression profiling. There are two commercially available products for whole blood RNA collection, PAXgene™ and Tempus™ blood collection tubes, and each comes with their own RNA purification method. In both systems the blood is immediately lysed when collected into the tube and RNA stabilized using proprietary reagents. Both systems enable minimal blood handling procedures thus minimizing the risk of inducing changes in gene expression through blood handling or processing. Because the RNA purification steps could influence the total RNA pool, we examined the impact of RNA isolation, using the PAXgene™ or Tempus™ method, on gene expression profiles.

Results

Using microarrays as readout of RNA from stimulated whole blood we found a common set of expressed transcripts in RNA samples from either PAXgene™ or Tempus™. However, we also found several to be uniquely expressed depending on the type of collection tube, suggesting that RNA purification methods impact results of differential gene expression profiling. Specifically, transcripts for several known PHA-inducible genes, including IFNγ, IL13, IL2, IL3, and IL4 were found to be upregulated in stimulated vs. control samples when RNA was isolated using the ABI Tempus™ method, but not using the PAXgene™ method (p < 0.01, FDR corrected). Sequenom Quantiative Gene Expression (QGE) (SanDiego, CA) measures confirmed IL2, IL4 and IFNγ up-regulation in Tempus™ purified RNA from PHA stimulated cells while only IL2 was up-regulated using PAXgene™ purified (p < 0.05).

Conclusion

Here, we demonstrate that peripheral blood RNA isolation methods can critically impact differential expression results, particularly in the clinical setting where fold-change differences are typically small and there is inherent variability within biological cohorts. A modified method based upon the Tempus™ system was found to provide high yield, good post-hybridization array quality, low variability in expression measures and was shown to produce differential expression results consistent with the predicted immunologic effects of PHA stimulation.