bluuebunny/crossref_metadata_2025 huggingface dataset:
The Rationale for Intervention to Reduce the Risk of Coronary Heart Disease
Authors: Rippe James M. , Angelopoulos Theodore J. , Zukley Linda
Published: June 2007

Cardiovascular diseases remain extremely common and the United States and are the single most common cause for death in both men and women. Many risk factors including cigarette smoking, elevated cholesterol, high blood pressure, obesity and in inactive lifestyle carry a significant lifestyle component. This fact is recognized in the National Guidelines for the Treatment of many risk factors for cardiovascular disease. Moreover, lifestyle intervention, in combination with proper medical and/or surgical therapy can play a significant role in the management of existing cardiovascular disease. In this review, we provide background and rationale for interventions to reduce the risk of coronary heart disease with a particular emphasis on intervening to improve lifestyle related issues. To achieve the best outcomes clinicians must be skilled not only in pharmacologic and surgical therapies but also in counseling patients on various lifestyle interventions to lower the risk of cardiovascular disease.
Risk Communication During Screening for Genomic Breast Cancer Susceptibility
Authors: Gramling Robert E. , Vidrine Jennifer Irvin
Published: June 2007

Screening for genomic predisposition to diseases of adulthood is emerging in standard medical practice. Breast cancer predisposition testing provides a useful example for understanding the potential implications of risk-related screening in practice. Risk is an important and complex psychological construct that is understood differently both between scientific disciplines and between medical and lay persons. The process of establishing thresholds for classifying whether one's risk reaches levels warranting departure from standard preventive strategies is an important predictor of both physician feedback and patient interpretation of their risk. Messages about genomic breast cancer risk arising during the pedigree screening context are conveyed via explicit and implicit modes of communication. Best practices for communicating about genomic risk and the implications for health disparities related to screening for genomic susceptibility remain unknown. More work is urgently needed given the societal forces that are catalyzing population-based screening for genomic predisposition into the routine practice of preventive medicine.
The Theological Accoutrements of Anti-Pluralism: The Confused Fate of American Episcopalianism
Authors: Radner Ephraim
Published: June 2007

This article examines the theological and ecclesial tensions that resulted from transplanting the established episcopalian polity and vision of the Church of England within the context of an evolving religious pluralism in America. The theological integralism of Anglican self-understanding as a result was forced to adjust itself in different and still uncomfortable ways within American Episcopalianism, and subsequent limitations on and inner conflicts within Anglican life in the United States (and beyond) are tied in part to these still unresolved tensions.
William Stringfellow's Sacramental Vision
Authors: Dackson Wendy
Published: June 2007

William Stringfellow (1929–85) was an Episcopal layman, attorney and social activist. Although much has been written about him since his death, most of it is in the form of personal testimony. Examinations of various doctrinal areas of his theological writings are unusual. Therefore, this article examines Stringfellow's idea of sacramental reality and grounds it in the worship of the Church and Christian engagement with the world. The concluding comments offer a justification for seeing this vision as one of enduring importance for faith and action in a post-Christian society.
Agreeing on a Common Accountability: What Can the Anglican Communion Learn from Ernst Troeltsch?
Authors: Frame Tom
Published: June 2007

In the light of recent theological controversies, the Anglican Communion urgently needs what Archbishop Rowan Williams has described as an ‘agreement over a common accountability’. Such an agreement must differentiate the things that define the essence of the Anglican Church from those that merely imparta distinctive cultural flavour. It will be built on a nuanced theological debate involving questions of self-definition that recognize the social, economic, political and cultural contexts enveloping the Communion's various national churches. In the same way that social structures and economic conditions bear directly upon the shape of religious organizations, it will become apparent that political pressures and cultural mores influence doctrinal commitments. The church-sect-mystic group typology developed by Ernst Troeltsch has the potential to help the Anglican Communion understand the origins of its theological diversity as part of a larger project that seeks to maintain corporate identity and to preserve organizational unity. His attempts to define the ‘essence of Christianity’ in the context of what might otherwise seem random, chaotic and possibly irreconcilable responses to Christ's teaching offers some interpretative insights that will assist Anglicans achieve a consensus on which ‘agreement over a common accountability’ might be based.
Neither Generalism nor Particularism: Ethical Correctness is Located in General Ethical Theories
Authors: Singleton Jane
Published: June 2007

In this article I shall be supporting two main claims. The first is that the essence of the difference between particularism and generalism lies in where they locate ethical correctness. The second is that generalism, although to be preferred to particularism, is not the final resting place for ethical correctness. Ultimately, ethical correctness resides in ethical theories that provide the rationale for generalism. Particularism is presented as a theory that allows attention to be paid to specific cases and shows a sensitivity to the particular case. Generalism, with its appeal to moral principles, is supposed to lack this sensitivity to specific cases. I argue that although this might be true of subsumptive generalism, it is not true of what I call judgmental generalism. This latter type of generalism retains an appeal to moral principles whilerequiringsensitivity to the particular case. I consider Kantian ethics as an example of this sort of generalism. Furthermore, I support the claim that this judgmental generalism is to be preferred to particularism. I argue against a prominent form of particularism, put forward by Jonathan Dancy, based on an appeal to the holism of reasons. This doctrine involves the claim that the value of a complex whole is not necessarily identical with the value of its parts. I show that Dancy’s discussion of this involves inconsistencies and also appears to incorporate subsumptive generalism. This statement of particularism is ultimately incoherent.
Taking the Distinction between Persons Seriously
Authors: Laden Anthony
Published: June 2007

Rawls criticizes utilitarianism for not taking the distinction between persons seriously, and suggests that his own theory: justice as fairness, does. I argue that justice as fairness aims to take the distinction seriously at four levels, ranging from the content of its principles to its conception of political philosophy, and that doing so at each stage is of fundamental importance in working out the basis of a conception of justice for a democratic society. Understanding Rawls’s theory in this way points to a clearer understanding of how to go on doing political philosophy after Rawls.
Rawls and Feminism: What Should Feminists Make of Liberal Neutrality?
Authors: Brake Elizabeth
Published: June 2007

I argue that Rawls’s liberalism is compatible with feminist goals. I focus primarily on the issue of liberal neutrality, a topic suggested by the work of Catharine MacKinnon. I discuss two kinds of neutrality: neutrality at the level of justifying liberalism itself, and state neutrality in political decision-making. Both kinds are contentious within liberal theory. Rawls’s argument for justice as fairness has been criticized for non-neutrality at the justificatory level, a problem noted by Rawls himself in Political Liberalism. I will defend a qualified account of neutrality at the justificatory level, taking an epistemic approach to argue for the exclusion of certain doctrines from the justificatory process. I then argue that the justification process I describe offers a justificatory stance supportive of the feminist rejection of state-sponsored gender hierarchy. Further, I argue that liberal neutrality at the level of political decision-making will have surprising implications for gender equality. Once the extent of the state’s involvement in the apparently private spheres of family and civil society is recognized, and the disproportionate influence of a sexist conception of the good on those structures—and concomitant promotion of that ideal—is seen, state neutrality implies substantive change. While—as Susan Moller Okin avowed—Rawls himself may have remained ambiguous on how to address gender inequality, his theory implies that the state must seek to create substantive, not merely formal, equality. I suggest that those substantive changes will not conflict with liberal neutrality but instead be required by it.
Public Reason and the Moral Foundation of Liberalism
Authors: Mahoney Jon
Published: June 2007

I argue against Rawls’s freestanding conception of liberalism. On my view, the moral foundation of liberalism can be defended in one of three ways: (1) as a conception one accepts as a result of one’s affirmation of political liberalism, (2) as a conception one must affirm as a presupposition for political liberalism, or (3) as a philosophical truth about practical reason and persons. The first option makes it impossible to distinguish a moral consensus from a modus vivendi. The second renders the moral foundation of liberalism dogmatic because it affirms a moral foundation for which no justification is provided. Since there are good reasons for rejecting (1) and (2), that leaves option (3). I argue that (3) should be the preferred option for liberals who advance liberalism as a political doctrine with a moral foundation.
Self-Realization and the Priority of Fair Equality of Opportunity
Authors: Taylor Robert
Published: June 2007

The lexical priority of fair equality of opportunity in John Rawls’s justice as fairness, which has been sharply criticized by Larry Alexander and Richard Arneson among others, is left almost entirely undefended in Rawls’s works. I argue here that this priority rule can be successfully defended against its critics despite Rawls’s own doubts about it. Using the few textual clues he provides, I speculatively reconstruct his defense of this rule, showing that it can be grounded on our interest in self-realization through work. This reconstructed defense makes liberal use of concepts already present in A Theory of Justice, including the Aristotelian Principle (which motivates the achievement of increasing virtuosity) and the Humboldtian concept of social union (which provides the context for the development of such virtuosity). I also show that this commitment to self-realization, far from violating the priority of right in Rawls’s theory, stems directly from his underlying commitment to autonomy, which is the very foundation of the moral law in his doctrine of right. The reconstituted defense of this priority rule not only strengthens the case for justice as fairness but also has important and controversial implications for public policy.
Good but Not Required?—Assessing the Demands of Kantian Ethics
Authors: Timmermann Jens
Published: June 2007

There seems to be a strong sentiment in pre-philosophical moral thought that actions can be morally valuable without at the same time being morally required. Yet Kant, who takes great pride in developing an ethical system .rmly grounded in common moral thought, makes no provision for any such extraordinary acts of virtue. Rather, he supports a classi.cation of actions as either obligatory, permissible or prohibited, which in the eyes of his critics makes it totally inadequate to the facts of morality. The related idea of uncommonly grand and noble deeds is frequently dismissed by Kant as high-.own emotional nonsense. Such considerations give rise to the fear that actions intuitively classed as morally commendable but not required must be re-classi.ed as commands of duty by Kant, making his ethical theory as unbearably demanding as direct utilitarianism. The paper divides into three sections: (1) an examination of the nature of moral goodness from a meta-ethical angle that introduces some passages from Kant's writings presenting strong theoretical evidence against the case for supererogatory action; (2) a critique of Thomas Hill's suggestion that within the category of wide duty we can accommodate some of the main features of actions classi.ed as supererogatory in other ethical systems; concluding that,contraHill, there are no actions of wide duty that can be so characterized in any signi.cant sense; and (3) a .nal discussion of the problem of how demanding the requirements of Kantian ethical theory really are.
Legal Reasons: Between Universalism and Particularism
Authors: Redondo María
Published: June 2007

The first part of this work analyses the universalist and the particularist conceptions of reasons. The second part projects this analysis to the legal domain. The author stresses that universalism and particularism regarding reasons are mutually exclusive theories linked to incompatible conceptions of norms, i.e. norms as strict universal conditionals and norms as defeasible conditionals. In giving an account of this tenet, different meanings of universality and defeasibility are explored. A parallel debate regarding reasons can be found in the legal domain, where two contrasting categories of norms are usually distinguished: rules and principles. On this issue the author argues that the conception of legal reasons depends on the way in which this contrast between different kinds of legal norms is shaped.
Keeping Our Distance in Compassion-Based Social Relations
Authors: Smith Steven
Published: June 2007

Although responding to ‘bad luck’ through instituting appropriate redistributive principles is a proper part of what justice entails, these principles must also paradoxically include the possibility of an agent-based response to misfortune that transforms adverse contingencies, such that the initial ‘bad luck’ becomes a positive part of the ‘sufferer's’ identity. This neo-Kantian accommodation within theories of justice signifies a ‘deep’ egalitarian empathic connectedness between persons, based on an equal respect for persons as agents (and not simply as passive victims of misfortune). Moreover, it is an accommodation that (a) can promote equality as ‘an end in itself’ rather than as merely a means to the end of enhancing a teleological conception of ‘well-being’ and ‘human flourishing’ and (b) can underpin a more robust Rawlsian conception of ‘justice as reciprocity’ than is usually allowed.
Chronically ill rural women: self-identified management problems and solutions
Authors: Cudney Shirley , Sullivan Therese , Winters Charlene A. , Paul Lynn , Oriet Pat
Published: June 2007

Objective: To add to the knowledge base of illness management of chronically ill, rural women by describing the self-identified problems and solutions reported by women participants in the online health-education segment of the Women to Women (WTW) computer outreach project.

Methods: WTW is a research-based computer intervention providing health education and online peer support for rural women with chronic diseases. Messages posted to the online chat room were examined to determine the women's self-management problems and solutions.

Results: The self-identified problems were: (1) difficulties in carrying through on self-management programmes; (2) negative fears and feelings; (3) poor communication with care providers; and (4) disturbed relationships with family and friends. The self-identified solutions to these problems included problem-solving techniques that were tailored to the rural lifestyle. Although not all problems were `solvable', they could be `lived with' if the women's prescriptions for self-management were used.

Discussion: Glimpses into the women's day-to-day experiences of living with chronic illness gleaned from the interactive health-education discussions will give health professionals insights into the women's efforts to manage their illnesses. The data provide health professionals with information to heighten their sensitivity to their clients' day-to-day care and educational needs.
Chronic disease management in Australia: evidence and policy mismatch, with asthma as an example
Authors: Beilby Justin , Holton Christine
Published: June 2007

All Western countries are developing and implementing new models for managing asthma. In Australia, the Asthma 3+ Visit Plan was implemented in 2001—2002, with the aim of establishing a structured approach in general practice for people with moderate and severe asthma, within a fee-for-service system. Evidence is emerging that the uptake across general practice has been poor, with approximately 5% of eligible people being enrolled. The reasons for the poor uptake include such factors as an inability to identify people with asthma, general practitioners being too busy with other clinical priorities, and the lack of interest and understanding of the need for a structured approach for this disease. This mismatch between evidence and policy development needs to be rectified, if sustainable models of chronic disease care are to be firmly established in general practice.
Can interprofessional education make a difference in the care of people with chronic disease?
Authors: Ross Fiona , Harris Ruth
Published: June 2007

In recent years, there has been an increasing policy focus on the role of interprofessional education in healthcare. However, the literature emphasizes process rather than outcomes, with little that specifically relates interprofessional educational interventions to the care of people with long-term conditions. This article questions what we know about interprofessional interventions in the care of people with chronic disease, examines the evidence for and potential of interprofessional education in changing practice, and makes suggestions for further research.
The personal impact of rheumatoid arthritis on patients' identity: a qualitative study
Authors: Lempp Heidi , Scott David , Kingsley Gabrielle
Published: June 2007

Objective: To provide a detailed understanding of the direct personal experiences of living with rheumatoid arthritis (RA) and the impact of the illness upon patients' lives, to inform the improvement of clinical care and training.

Method: A qualitative study was performed using data from semi-structured interviews with 26 patients who live with RA, recruited at two outpatient clinics in south-east England.

Results: In addition to the physical impact of RA on patients' lives, their accounts gave detailed descriptions of how their identity was affected in relation to: (1) their private lives (e.g. difficulties in their relationships, or caring for others); (2) their public roles and responsibilities (e.g. in their paid work and in experiences of stigmatization or discrimination); and (3) their private and public domains (e.g. perceived change of physical appearance, alteration of self-image, and change or loss of social roles). Young patients (25—45 years) did report some differences in their chronic illness experiences, but patients from black and ethnic minorities did not.

Discussion: The study highlights new findings which can facilitate more open communication between staff and patients on the personal impact of RA, on patients' coping strategies, and on the effects on their identity both in private and in public. This will allow multidisciplinary outpatient services to provide care more closely matched to the difficulties that are directly experienced by patients.
`When I am together with them I feel more ill.' The stigma of multiple sclerosis experienced in social relationships
Authors: Grytten Nina , Måseide Per
Published: June 2007

Objectives: We explored the stigma that people with multiple sclerosis (MS) experienced in social relationships. Informed by the symbolic integrationist paradigm, this sociological study focuses on the creation of personal identity through interaction with others. The symbolic interactionist account of stigma examines the meaning and reality being negotiated in communication with others.

Methods: Fourteen people with MS and their relatives were interviewed. The unstructured interviews were tape-recorded, transcribed and coded in accordance with the procedure of grounded theory.

Results: Informants reported being ignored or, in contrast, having people overemphasize MS in interpersonal encounters. Although people tried to act tactfully, these acts were experienced as crucial stigmatizing. Informants were coping to counteract stigmatizing experiences in social relationships.

Discussion: People with MS perceive that their bodily performance and impression management is being judged in interpersonal encounters. Being ignored or perceiving that MS is overemphasized indicates the dilemma of managing stigma in social networks. Consequently, during interaction and in social relationships, people with MS experience a sense of `feeling more ill'. This paper describes strategies of networking to affirm self and identity.
Remaking the future: contemplating a life with chronic widespread pain
Authors: Richardson Jane C. , Bie Nio Ong  , Sim Julius
Published: June 2007

Objectives: This paper reports findings from a larger study that aimed to explore how people with chronic widespread pain experience, understand and make meaning of their `condition', and attempt to influence or exert control over their pain. This included an exploration of sufferers' understanding of the past and future as well as of their present situation.

Methods: A combination of data generation methods was used, including lifegrid interviews, diaries and diary interviews, with eight people with chronic widespread pain. Five family members also participated in interviews. Analytical methods were based on interpretative phenomenological analysis (IPA).

Results: With regard to their views about the future, participants could be categorized into those who were `optimistic' (`things can only get better'), those who were pessimistic (`things will get worse'), and those who were overwhelmed with uncertainty about the future. Uncertainty was a dominant feature in all the accounts of the future.

Discussion: The pervading uncertainty of chronic widespread pain, in which there is no framework for the trajectory of the condition, affects perceptions of the future and makes planning for the future difficult. The findings also raise the question of how this makes chronic widespread pain different from other chronic conditions in terms of understanding of chronicity, time and future, and hence `acceptance'.
Social support and self-management of type 2 diabetes among immigrant Australian women
Authors: Kokanovic Renata , Manderson Lenore
Published: June 2007

Objective: To elucidate the social meanings and interpretations that immigrant women attach to the diagnosis of type 2 diabetes, and the social support and professional advice that they receive following this diagnosis.

Methods: In-depth interviews were conducted with 16 immigrant women living in Melbourne, Australia, from communities with a higher than average incidence of type 2 diabetes. Women were recruited purposively through general practitioners and community organizations. The women's initial reaction to the diagnosis of diabetes, understandings of the behavioural changes required to control symptoms and prevent complications and the nature of the social and professional supports were discussed. Interviews were audio-taped, transcribed, coded and analysed thematically by both authors.

Results: Some women were critical of their doctors but also manipulated their encounters to avoid receiving unwelcome information about the progress of the disease and consequent required changes in management. Social interactions influenced women's adjustments to diagnosis and informed their communication and adaptation of their lives. Choice of support varied by cultural background, but many respondents reflected on the thin line between support and interference. All women found most understanding from others living with diabetes.

Discussion: The social context of people with type 2 diabetes is important in facilitating or inhibiting the management of the condition. Variations in attitudes to family and professionals influenced adherence to advice and emphasized the need for appropriate support to women to sustain behavioural change.
Projection, stereotyping, and the perception of chronic medical conditions
Authors: Veazie Peter J.
Published: June 2007

Objectives: To test the hypotheses that people with chronic medical conditions are more likely than those without chronic medical conditions to project personal characteristics onto the population with chronic medical conditions, and that people without chronic medical conditions are more likely to stereotype those with chronic medical conditions.

Methods: The study is a secondary analysis of the 2000 Chronic Illness and Caregiving survey conducted by Harris Interactive Inc. using linear and probit regressions.

Results: The hypothesis that persons with chronic medical conditions project their characteristics onto the population of those with chronic medical conditions is strongly supported. The hypothesis that persons without chronic medical conditions stereotype the population of those with chronic medical conditions is weakly supported.

Discussion: The findings imply that characterizations of persons with chronic medical conditions vary more among those with chronic medical conditions than among those without, and that those without chronic medical conditions have more homogeneous representations. This difference between those who have chronic medical conditions and those who do not implies a potential for greater variation in support for the particulars of policies addressing chronic medical conditions among those with chronic medical conditions.
On Evangelical Ecclesiology
Authors: Webster John
Published: June 2007

Evangelical ecclesiology describes the relation between the gospel and the church, and in particular the way in which the grace of the triune God constitutes the church as the communion of saints. Consequently: (1) The doctrine of the church is shaped by an account of the perfection of God, i.e. the sufficiency and fullness of God’s being and act. This perfection is not inclusive (as in some communion ecclesiologies), but is to be thought of as a movement of grace in which God determines himself for fellowship with his creatures. (2) The visibility of the church (pervasive in modern ecclesiology) is properly a spiritual visibility, which the church has by virtue of the Spirit’s act. The primary visible acts of the church are its attestations of the presence and action of God.
Barriers to Integrating Quantitative and Qualitative Research
Authors: Bryman Alan
Published: June 2007

This article is concerned with the possibility that the development of mixed methods research is being hindered by the tendency that has been observed by some researchers for quantitative and qualitative findings either not to be integrated or to be integrated to only a limited extent. It examines findings from 20 interviews with U.K. social researchers, all of whom are practitioners of mixed methods research. From these interviews, a wide variety of possible barriers to integrating mixed methods findings are presented. The article goes on to suggest that more attention needs to be given to the writing of mixed methods articles.
Thoracopagus Conjoined Twins
Authors: Ratner Amy N. , Terrone Dom , Cosgrove Facog Julie
Published: June 2007

Conjoined twins are identical twins who develop with a single placenta from a single fertilized ovum. The developing embryo begins to split after the 13th day of conception but stops part way, leaving the partially separated ovum to mature into a conjoined fetus. Conjoined twins may be joined at a variety of anatomic sites.
Diagnostic maging in an Outpatient Center
Authors: Marchand Keith
Published: June 2007

In the current health care environment, outpatient diagnostic imaging centers face intense competition for the declining health care dollar. One approach to providing health care services at low cost is to provide as many services as possible in the outpatient environment. Quality control and patient satisfaction are issues of major importance. The “vertical integration” model is becoming more prevalent, and the author contends that cooperative networking among outpatient centers may be a key to successful survival. The role of the sonographer in the changing health care environment is described. The increasing importance of accreditation and the emergence of a growing number of accrediting bodies, as well as the potential impact of the new ultrasound contrast agents, are discussed.
Genetic variants of chemokine receptor CCR7 in patients with systemic lupus erythematosus, Sjogren's syndrome and systemic sclerosis
Authors: Kahlmann Daniel , Davalos-Misslitz Ana Clara Marques , Ohl Lars , Stanke Frauke , Witte Torsten , Förster Reinhold
Published: June 2007

Background

The chemokine receptor CCR7 is a key organizer of the immune system. Gene targeting in mice revealed that Ccr7-deficient animals are severely impaired in the induction of central and peripheral tolerance. Due to these defects, Ccr7-deficient mice spontaneously develop multi-organ autoimmunity showing symptoms similar to those observed in humans suffering from connective tissue autoimmune diseases. However, it is unknown whether mutations of CCR7 are linked to autoimmunity in humans.

Results

DNA samples were collected from 160 patients suffering from connective tissue autoimmune disease (Sjogren's syndrome, n = 40; systemic lupus erythematosus, SLE, n = 20 and systemic sclerosis, n = 100) and 40 health subjects (n = 40). All participants in this study were of German descent. Samples were screened for single nucleotide polymorphisms (SNP) by sequencing the coding region of the CCR7 gene as well asthe exon flaking intron sites and parts of the regions encoding for the 5'- and 3'-UTR. CCR7 variants were rare. We identified six different sequence variants, which occurred in heterozygosis. The identified SNP were observed at position -60 C/T (observed 1x), +6,476 A/G (7x), +6,555 C/T (15x), +6,560 C/T (6x), +10,440 A/G (3x) and +11,475 C/A (1x). Four of these variants (+6,476 A/G, +6,555 C/T, +6,560 C/T and +10,440 A/G) display allelic frequencies between 1% and 5 % and were present in both patients and control groups. The variants +6,476 A/G, +6,555 C/T, +6,560 C/T are located in the intron 2, while the +10,440 A/G variant corresponds to a silent mutation in exon 3. The variants -60 C/T and +11,475 C/A which are located at the 5'-UTR and 3-UTR respectively, display allelic frequencies below 1%. No correlation between these variants and the autoimmune diseases investigated could be observed. However, reporter gene expression assay demonstrated that the mutation at the -60 C/T position in homozygosis leads to reduced luciferase activity.

Conclusion

These results suggest that variants of CCR7 gene occur at an extremely low frequency in the German population and that neither Sjogren's syndrome, systemic lupus erythematosus, nor systemic sclerosis are associated with these variants. Nevertheless, the decreased luciferase activity observed in cells transfected with the promoter region bearing the -60 C/T mutation suggests that this CCR7 variant could potentially lead to increased susceptibility to autoimmunity.
New data on robustness of gene expression signatures in leukemia: comparison of three distinct total RNA preparation procedures
Authors: Campo Dell'Orto Marta , Zangrando Andrea , Trentin Luca , Li Rui , Liu Wei-min , te Kronnie Geertruy , Basso Giuseppe , Kohlmann Alexander
Published: June 2007

Background

Microarray gene expression (MAGE) signatures allow insights into the transcriptional processes of leukemias and may evolve as a molecular diagnostic test. Introduction of MAGE into clinical practice of leukemia diagnosis will require comprehensive assessment of variation due to the methodologies. Here we systematically assessed the impact of three different total RNA isolation procedures on variation in expression data: method A: lysis of mononuclear cells, followed by lysate homogenization and RNA extraction; method B: organic solvent based RNA isolation, and method C: organic solvent based RNA isolation followed by purification.

Results

We analyzed 27 pediatric acute leukemias representing nine distinct subtypes and show that method A yields better RNA quality, was associated with more differentially expressed genes between leukemia subtypes, demonstrated the lowest degree of variation between experiments, was more reproducible, and was characterized with a higher precision in technical replicates. Unsupervised and supervised analyses grouped leukemias according to lineage and clinical features in all three methods, thus underlining the robustness of MAGE to identify leukemia specific signatures.

Conclusion

The signatures in the different subtypes of leukemias, regardless of the different extraction methods used, account for the biggest source of variation in the data. Lysis of mononuclear cells, followed by lysate homogenization and RNA extraction represents the optimum method for robust gene expression data and is thus recommended for obtaining robust classification results in microarray studies in acute leukemias.
Gene discovery for the carcinogenic human liver fluke, Opisthorchis viverrini
Authors: Laha Thewarach , Pinlaor Porntip , Mulvenna Jason , Sripa Banchob , Sripa Manop , Smout Michael J , Gasser Robin B , Brindley Paul J , Loukas Alex
Published: June 2007

Background

Cholangiocarcinoma (CCA) – cancer of the bile ducts – is associated with chronic infection with the liver fluke, Opisthorchis viverrini. Despite being the only eukaryote that is designated as a 'class I carcinogen' by the International Agency for Research on Cancer, little is known about its genome.

Results

Approximately 5,000 randomly selected cDNAs from the adult stage of O. viverrini were characterized and accounted for 1,932 contigs, representing ~14% of the entire transcriptome, and, presently, the largest sequence dataset for any species of liver fluke. Twenty percent of contigs were assigned GO classifications. Abundantly represented protein families included those involved in physiological functions that are essential to parasitism, such as anaerobic respiration, reproduction, detoxification, surface maintenance and feeding. GO assignments were well conserved in relation to other parasitic flukes, however, some categories were over-represented in O. viverrini, such as structural and motor proteins. An assessment of evolutionary relationships showed that O. viverrini was more similar to other parasitic (Clonorchis sinensis and Schistosoma japonicum) than to free-living (Schmidtea mediterranea) flatworms, and 105 sequences had close homologues in both parasitic species but not in S. mediterranea. A total of 164 O. viverrini contigs contained ORFs with signal sequences, many of which were platyhelminth-specific. Examples of convergent evolution between host and parasite secreted/membrane proteins were identified as were homologues of vaccine antigens from other helminths. Finally, ORFs representing secreted proteins with known roles in tumorigenesis were identified, and these might play roles in the pathogenesis of O. viverrini-induced CCA.

Conclusion

This gene discovery effort for O. viverrini should expedite molecular studies of cholangiocarcinogenesis and accelerate research focused on developing new interventions, drugs and vaccines, to control O. viverrini and related flukes.
Genetic relatedness among isolates of Shigella sonnei carrying class 2 integrons in Tehran, Iran, 2002–2003
Authors: Ranjbar Reza , Aleo Aurora , Giammanco Giovanni M , Dionisi Anna Maria , Sadeghifard Nourkhoda , Mammina Caterina
Published: June 2007

Background

Shigella spp. are major cause of diarrhoeal disease in both developing and developed countries. Shigella sonnei is the serogroup of Shigella most frequently responsible for sporadic and epidemic enteritis in developed countries. In recent years the emergence and spread of S. sonnei biotype g carrying class 2 integron have been frequently reported in many countries. Recently, S. sonnei has been reported as the prevalent serogroup of Shigella in Iran.

The present study was carried out to investigate phenotypic and genetic characteristics of Shigella sonnei isolates identified in the years 2002 and 2003 in Tehran, Iran.

Methods

Biotyping, drug susceptibility testing, pulsed field gel electrophoresis (PFGE) and analysis of class 2 integrons have been carried out on 60 S. sonnei isolates, including 57 sporadic isolates from paediatric cases of shigellosis occurring in 2002 and 2003, two sporadic isolates recovered in 1984 and the ATCC 9290 strain.

Results

Biotype g and resistance to streptomycin, sulfamethoxazole-trimethoprim and tetracycline were exhibited by 54 of the 57 recent isolates. Of the 54 biotype g isolates, 28 exhibited a class 2 integron of 2161 bp, and 24 a class 2 integron of 1371 bp, respectively. Class 2 integrons were not detected in four isolates only, including the two endemic isolates recovered in 1984 and two strains from recent sporadic cases. PFGE divided the strains into eight pulsotypes labeled A to H, three major pulsotypes – A to C – including the large majority of the recent sporadic S. sonnei isolates. Pulsotypes A and C were the most prevalent groups, accounting for 41.6% and 35.0%, respectively, of the isolates under study.

Conclusion

The results suggest that biotype g, class 2 integron carrying S. sonnei are prevalent in our geographic area. S. sonnei isolated in the years 2002 and 2003 could be attributed to a few predominant clusters including, respectively, strains with pulsotypes B and C carrying a 2161 bp class 2 integron, and those having pulsotype A and a 1371 bp class 2 integron. A few epidemic clones are responsible for the apparently endemic occurrence of shigellosis in Tehran, Iran.
Knowledge translation on dementia: a cluster randomized trial to compare a blended learning approach with a "classical" advanced training in GP quality circles
Authors: Vollmar Horst C , Butzlaff Martin E , Lefering Rolf , Rieger Monika A
Published: June 2007

Background

Thus far important findings regarding the dementia syndrome have been implemented into patients' medical care only inadequately. A professional training accounting for both, general practitioners' (GP) needs and learning preferences as well as care-relevant aspects could be a major step towards improving medical care. In the WIDA-study, entitled "Knowledge translation on dementia in general practice" two different training concepts are developed, implemented and evaluated. Both concepts are building on an evidence-based, GP-related dementia guideline and communicate the guideline's essential insights.

Methods/Design

Both development and implementation emphasize a procedure that is well-accepted in practice and, thus, can achieve a high degree of external validity. This is particularly guaranteed through the preparation of training material and the fact that general practitioners' quality circles (QC) are addressed. The evaluation of the two training concepts is carried out by comparing two groups of GPs to which several quality circles have been randomly assigned. The primary outcome is the GPs' knowledge gain. Secondary outcomes are designed to indicate the training's potential effects on the GPs' practical actions. In the first training concept (study arm A) GPs participate in a structured case discussion prepared for by internet-based learning material ("blended-learning" approach). The second training concept (study arm B) relies on frontal medical training in the form of a slide presentation and follow-up discussion ("classical" approach).

Discussion

This paper presents the outline of a cluster-randomized trial which has been peer reviewed and support by a national funding organization – Federal Ministry of Education and Research (BMBF) – and is approved by an ethics commission. The data collection has started in August 2006 and the results will be published independently of the study's outcome.

Trial Registration

Current Controlled Trials [ISRCTN36550981]
Regulation of Prohormone Convertases in Hypothalamic Neurons: Implications for ProThyrotropin-Releasing Hormone and Proopiomelanocortin
Authors: Nillni Eduardo A.
Published: June 2007

Recent evidence demonstrated that posttranslational processing of neuropeptides is critical in the pathogenesis of obesity. Leptin or other physiological changes affects the biosynthesis and processing of many peptides hormones as well as the regulation of the family of prohormone convertases responsible for the maturation of these hormones. Regulation of energy balance by leptin involves regulation of several proneuropeptides such as proTRH and proopiomelanocortin. These proneuropeptide precursors require for their maturation proteolytic cleavage by the prohormone convertases 1 and 2 (PC1/3 and PC2). Because biosynthesis of mature peptides in response to leptin requires prohormone processing, it is hypothesized that leptin might regulate hypothalamic PC1/3 and PC2 expression, ultimately leading to coordinated processing of prohormones into mature peptides. Leptin has been shown to increase PC1/3 and PC2 promoter activities, and starvation of rats, leading to low serum leptin levels, resulted in a decrease in PC1/3 and PC2 gene and protein expression in the paraventricular and arcuate nucleus of the hypothalamus. Changes in nutritional status also changes proopiomelanocortin processing in the nucleus of the solitary tract, but this is not reversed by leptin. The PCs are also physiologically regulated by states of hyperthyroidism, hyperglycemia, inflammation, and suckling, and a recently discovered nescient helix-loop-helix-2 transcription factor is the first one to show an ability to regulate the transcription of PC1/3 and PC2. Therefore, the coupled regulation of proneuropeptide/processing enzymes may be a common process, by which cells generate more effective processing of prohormones into mature peptides.
Aldose Reductase-Regulated Tumor Necrosis Factor-α Production Is Essential for High Glucose-Induced Vascular Smooth Muscle Cell Growth
Authors: Ramana Kota V. , Tammali Ravinder , Reddy Aramati B. M. , Bhatnagar Aruni , Srivastava Satish K.
Published: June 2007

Diabetes is associated with increased generation of cytokines and tissue inflammation, but it is unclear how increased cytokine synthesis is causally related to the development of diabetic complications. Here, we report that exposure to high (25 mm) glucose, but not iso-osmotic concentrations of mannitol or 3-methyl glucose, increased TNF-α secretion by rat and human aortic smooth muscle cells in culture. The increase in TNF-α production was prevented by actinomycin D and cycloheximide, indicating transcriptional activation of TNF-α gene. High glucose (HG)-induced TNF-α release was specifically inhibited by protein kinase C (PKC)-δ inhibitor (Rottlerin; EMD Biosciences, San Diego, CA), but not PKC-β2 inhibitor (CGP53353; Tocris Cookson Inc., Ellisville, MO), indicating the possible involvement of PKC-δ in HG signaling. TNF-α secretion was also prevented by pretreating cells with aldose reductase (AR) inhibitors, sorbinil or tolrestat and in cells treated with antisense AR mRNA. Inhibition of AR also prevented the increase in TNF-α mRNA. Addition of anti-TNF-α antibodies or soluble TNF-α receptors 1 and 2 to the medium or RNA interference ablation of TNF-α attenuated nuclear factor-κB activation and prevented HG-stimulated cell growth. These data indicate that AR is required for HG-induced TNF-α synthesis and release. In vivo, the release of TNF-α by HG leading to autocrine stimulation of TNF-α synthesis may be a critical step in the development of the cardiovascular complications of diabetes. Interruption of the autocrine effects of TNF-α may be a useful strategy for treating diabetic vasculopathies.
Cold Exposure Increases the Biosynthesis and Proteolytic Processing of Prothyrotropin-Releasing Hormone in the Hypothalamic Paraventricular Nucleus via β-Adrenoreceptors
Authors: Perello Mario , Stuart Ronald C. , Vaslet Charles A. , Nillni Eduardo A.
Published: June 2007

Different physiological conditions affect the biosynthesis and processing of hypophysiotropic proTRH in the hypothalamic paraventricular nucleus, and consequently the output of TRH. Early studies suggest that norepinephrine (NE) mediates the cold-induced activation of the hypothalamic-pituitary-thyroid axis at a central level. However, the specific role of NE on the biosynthesis and processing of proTRH has not been fully investigated. In this study, we found that NE affects gene transcription, protein biosynthesis, and secretion in TRH neurons in vitro; these changes were coupled with an up-regulation of prohormone convertase enzymes (PC) 1/3 and PC2. In vivo, NE is the main mediator of the cold-induced activation of the hypothalamic-pituitary-thyroid axis at the hypothalamic level, in which it potently stimulates the biosynthesis and proteolytic processing of proTRH through a coordinated up-regulation of the PCs. This activation occurs via β-adrenoreceptors and phosphorylated cAMP response element binding signaling. In contrast, α-adrenoreceptors regulate TRH secretion but not proTRH biosynthesis and processing. Therefore, this study provides novel information on the molecular mechanisms of control of hypophysiotropic TRH biosynthesis.
Effect of base modifications on structure, thermodynamic stability, and gene silencing activity of short interfering RNA
Authors: Sipa Katarzyna , Sochacka Elzbieta , Kazmierczak-Baranska Julia , Maszewska Maria , Janicka Magdalena , Nowak Genowefa , Nawrot Barbara
Published: June 2007

A series of nucleobase-modified siRNA duplexes containing “rare” nucleosides, 2-thiouridine (s2U), pseudouridine (Ψ), and dihydrouridine (D), were evaluated for their thermodynamic stability and gene silencing activity. The duplexes with modified units at terminal positions exhibited similar stability as the nonmodified reference. Introduction of the s2U or Ψ units into the central part of the antisense strand resulted in duplexes with higher melting temperatures (Tm). In contrary, D unit similarly like wobble base pair led to the less stable duplexes (ΔTm 3.9 and 6.6°C, respectively). Gene-silencing activity of siRNA duplexes directed toward enhanced green fluorescent protein or beta-site APP cleaving enzyme was tested in a dual fluorescence assay. The duplexes with s2U and Ψ units at their 3′-ends and with a D unit at their 5′-ends (with respect to the guide strands) were the most potent gene expression inhibitors. Duplexes with s2U and Ψ units at their 5′-ends were by 50% less active than the nonmodified counterpart. Those containing a D unit or wobble base pair in the central domain had the lowest Tm, disturbed the A-type helical structure, and had more than three times lower activity than their nonmodified congener. Activity of siRNA containing the wobble base pair could be rescued by placing the thio-nucleoside at the position 3′-adjacent to the mutation site. Thermally stable siRNA molecules containing several s2U units in the antisense strand were biologically as potent as their native counterparts. The present results provide a new chemical tool for modulation of siRNA gene-silencing activity.