Psychiatric disorders present distinct clinical challenges which are partly attributable to their multifactorial aetiology and the absence of laboratory tests that can be used to confirm diagnosis or predict risk. Psychiatric disorders are highly heritable, but also polygenic, with genetic risk conferred by interactions between thousands of variants of small effect that can be summarized in a polygenic risk score. We discuss four areas in which the use of polygenic risk scores in psychiatric research and clinical contexts could have ethical (...) implications. First, there is concern that clinical use of polygenic risk scores may exacerbate existing health inequities. Second, research findings regarding polygenic risk could be misinterpreted in stigmatising or discriminatory ways. Third, there are concerns associated with testing minors as well as eugenics concerns elicited by prenatal polygenic risk testing. Fourth, potential challenges that could arise with the feedback and interpretation of high polygenic risk for a psychiatric disorder would require consideration. While there would be extensive overlap with the challenges of feeding back genetic findings in general, the potential clinical use of polygenic risk scoring warrants discussion in its own right, given the recency of this possibility. To this end, we discuss how lay interpretations of risk and genetic information could intersect. Consideration of these factors would be necessary for ensuring effective and constructive communication and interpretation of polygenic risk information which, in turn, could have implications for the uptake of any therapeutic recommendations. Recent advances in polygenic risk scoring have major implications for its clinical potential, however, care should be taken to ensure that communication of polygenic risk does not feed into problematic assumptions regarding mental disorders or support reductive interpretations. (shrink)

BackgroundCommunity engagement within biomedical research is broadly defined as a collaborative relationship between a research team and a group of individuals targeted for research. A Community Advisory Board is one mechanism of engaging the community. Within genomics research CABs may be particularly relevant due to the potential implications of research findings drawn from individual participants on the larger communities they represent. Within such research, CABs seek to meet instrumental goals such as protecting research participants and their community from research-related risks, (...) as well as intrinsic goals such as promoting the respect of participants and their community. However, successful community engagement depends on the degree to which CABs legitimately represent and engage with communities targeted for research. Currently, there is little literature describing the use of CABs in genomics research taking place in developing countries, and even less in the field of genomics research relating to mental illness. The aim of this article is to describe and consider the contributions made by a researcher-driven, population-specific CAB in a genomics of schizophrenia research project taking place in South Africa, from the perspective of the research team.DiscussionFour broad discussion topics emerged during the CAB meetings namely: 1) informed consent procedures, 2) recruitment strategies, 3) patient illness beliefs and stigma experiences, and 4) specific ethical concerns relating to the project. The authors consider these discussions in terms of their contributions to instrumental and intrinsic goals of community engagement.SummaryThe CAB gave valuable input on the consent processes and materials, recruitment strategies and suggested ways of minimizing the potential for stigma and discrimination. All of these contributions were of an instrumental nature, and helped improve the way in which the research took place. In addition, and perhaps more importantly, the CAB made a unique and important contribution relating to intrinsic functions such as promoting the respect and dignity of research participants and their community. This was particularly evident in ensuring sensitivity and respect of the community’s traditional beliefs about schizophrenia and its treatment, and in this way promoting a respectful relationship between the research team and the participants. (shrink)

Preparing the Next Generation of Oral Historians is an invaluable resource to educators seeking to bring history alive for students at all levels. Filled with insightful reflections on teaching oral history, it offers practical suggestions for educators seeking to create curricula, engage students, gather community support, and meet educational standards. By the close of the book, readers will be able to successfully incorporate oral history projects in their own classrooms.

In recent years, cognitive neuroscientists have began to explore the process of how sensory information gains access to awareness. To further probe this process, event-related functional magnetic resonance imaging was used while testing subjects with a paradigm known as the “attentional blink.” In this paradigm, visually presented information sporadically fails to reach awareness. It was found that the magnitude and time course of activation within the anterior cingulate , medial prefrontal cortex , and frontopolar cortex predicted whether or not information (...) was consciously perceived during the critical period for the attentional blink. These results are discussed in light of a neural framework for conscious processing. (shrink)

Theories of distributive justice are most severely tested in the area of disability. In this book, Mark Stein argues that utilitarianism performs better than egalitarian theories in this area: whereas egalitarian theories help the disabled either too little or too much, utilitarianism achieves the proper balance by placing resources where they will do the most good. Stein offers what may be the broadest critique of egalitarian theory from a utilitarian perspective. He addresses the work of egalitarian theorists John (...) Rawls, Ronald Dworkin, Amartya Sen, Bruce Ackerman, Martha Nussbaum, Norman Daniels, Philippe Van Parijs, and others. Stein claims that egalitarians are often driven to borrow elements of utilitarianism in order to make their theories at all plausible. The book concludes with an acknowledgment that both utilitarians and egalitarians face problems in the distribution of life-saving medical resources. Stein advocates a version of utilitarianism that would distribute life-saving resources based on life expectancy, not quality of life. Egalitarian theories, he argues, ignore life expectancy and so are again found wanting. _Distributive Justice and Disability _is a powerful and engaging book that helps to reframe the debate between egalitarian and utilitarian thinkers. (shrink)

In this essay, I offer a utilitarian perspective on humanitarian intervention. There is no generally accepted precise definition of the term ‘humanitarian intervention’. I will provisionally, and roughly, define humanitarian intervention as the use of force by a state, beyond its own borders, that has as a purpose or an effect the protection of the human rights of noncitizens or the reduction of the suffering of noncitizens.

Utilitarianism is more convincing than resource egalitarianism or welfare egalitarianism as a theory of how resources should be distributed between disabled people and nondisabled people. Unlike resource egalitarianism, utilitarianism can redistribute resources to the disabled when they would benefit more from those resources than nondisabled people. Unlike welfare egalitarianism, utilitarianism can halt redistribution when the disabled would no longer benefit more than the nondisabled from additional resources. -/- The author considers one objection to this view: it has been argued, by (...) Sen and others, that there are circumstances under which utilitarianism would unfairly distribute fewer resources to the physically disabled than to nondisabled people, on the ground that the disabled would derive less benefit from those resources. In response, the author claims that critics of utilitarianism have fallaciously exaggerated the circumstances under which the disabled would benefit less than the nondisabled from additional resources. In those limited circumstances in which the disabled really would benefit less from resources, the author argues, it does not seem unfair to distribute fewer resources to them. (shrink)

There is now a wealth of information that histone proteins play a primary role in the structural and transcriptional properties of chromatin, the protein‐DNA complex which constitutes the eukaryotic genome1, 2. In light of the crucial role of histones in cellular function, it is not surprising that their structural genes are found to be controlled in conjunction with the cell cycle, with the synthesis of most histones tightly coupled to nuclear DNA replication. The evidence suggests that this linkage between DNA (...) replication and histone synthesis involves the regulated adjustment of histone mRNA levels through both transcriptional and posttranscriptional control process. The possible mechanisms underlying these diverse control processes are described here. (shrink)

_Cultures and Identities in Transition_ returns to the roots of analytical psychology, offering a thematic approach which looks at personal and cultural identities in relation to Jung’s own identity and the identities of contemporary Jungians. The book begins with two clinical studies, representing a meeting point between the traditional praxis of Jungian analysis, on the one side, and the current zeitgeist, world events and collective anxieties as impacting on persons in therapy, on the other. An international range of expert contributors (...) go on to discuss topics including: issues of national and personal identity – looking back to a shared history and forward to novel applications of Jungian ideas. Jung’s cross-disciplinary dialogues with Victor White. what the designation "Jungian" actually means. Based on papers given at the joint IAAP and IAJS conference held in Zurich in 2008, this book will be essential reading for all Jungians. (shrink)

Most U.S. jurisdictions deem testimony regarding what one spouse tells the other in private inadmissible in most circumstances and most do not allow a person to be compelled to testify against his or her spouse. Although confidential communications and what a spouse knows about the other are both relevant and quite probative, triers of fact do not get to consider them. The scope, character, and very existence of these exceptions to the general principle of admitting everything into evidence have been (...) questioned by legal commentators for centuries, but they remain in force in most U.S. jurisdictions. This paper reviews the justifications for the spousal evidentiary privileges and argues for recasting the spousal evidentiary privileges in functional terms. (shrink)

Falk's hominin mother-infant model presupposes an emerging infant capacity to perceive and learn from afforded gestures and vocalizations. Unlike back-riding offspring of other primates, who were in no need to decenter their own body-centered perspective, a mirror neurons system may have been adapted in hominin infants to subserve the kind of (m)other-centered mirroring we now see manifested by human infants soon after birth.

What are the conditions required for becoming better human beings? What are our limitations and possibilities? I understand “becoming better” as a combined improvement process bringing persons “up from” a negative condition and “up to” a positive one. Today there is a tendency to understand improvement in a one-sided way as a movement up to the mastery of cognitive skills, neglecting the negative conditions that can make these skills mis-educative. I therefore tell six stories in the Western tradition about conditions (...) for a combined improvement process. The first three stories belong to our cultural ABC: an Aristotelian story about moral wisdom which brings people up from being enslaved by passions and up to a good life of virtues; a Biblical story about God’s word bringing listeners up from a self-centred life and up into creative work as God’s fellow workers, and a short Cave story by Plato about liberation—up from living by common illusions and up to enlightenment from what is perfectly good. The subsequent three stories interpret and actualise these basic stories in different ways: a story about moral wisdom and divine love (Thomas Aquinas), a story about individual freedom and rationality (Immanuel Kant), and a story about the love that builds us up as equal human beings (Søren Kierkegaard). These stories may directly guide us adults—and indirectly the children and youth who learn from our examples—when we struggle to become better human beings. (shrink)

Children as learners need adults who love them, even when the children are unable to give anything in return. Furthermore, adults should be able to make wise judgements concerning what is good for the children. The clarification of these principles and of their educational import has to start within our own cultural tradition. Agape (unconditional love, neighbour-love or charity) is a basic concept in the Christian tradition. Phronesis (moral wisdom, practical judgement or prudence) has a key position in the Aristotelian (...) tradition. In his Summa TheologiaeThomas Aquinas has combined these traditions and ethical concepts, with agape (in Latin caritas) as the commanding concept. The article will explore some key challenges and productive resources revealed by this combination for today's education and upbringing. (shrink)

In lieu of an abstract, here is a brief excerpt of the content:Philosophy, Psychiatry, & Psychology 12.3 (2005) 261-263 [Access article in PDF] The Philosophy of Evil Dan J. Stein Keywords philosophy, evil, self-deception, psychopathy, narcissism, sadism Kubarych (2005) first draws on Peck (1983) to suggest a distinction between psychopaths who have no conscience and therefore no need for self-deception, and evil narcissists who use self-deception to keep the emotional consequences of their crimes out of awareness. He then draws (...) on Davidson (1985) to emphasize a parallel between self-deception (or weakness of the warrant) where an irrational belief conflicts with the evidence, and akrasia (or weakness of the will) where an irrational intention is in conflict with one's values.Although self-deception has long been de-scribed and debated (Fingarette 2000; McLaughlin and Rorty 1988; Mele 2001), a cognitive-affective neuroscience of self-deception has become possible only recently. Such an approach includes several strands. First, contemporary information processing constructs (e.g., schemas) have been used to reframe the early insights of writers like Freud and James, and to emphasize how inattention to painful truths provide a shield against anxiety (Goleman 1997). Second, the theoretical framework of evolutionary psychology has been used to emphasize the adaptive advantages of self-deception (Lockard and Delroy 1988). Third, functional brain imaging studies have noted increased activity in executive regions (e.g., prefrontal and anterior cingulate cortices) during attempted deception but not during truthful responding, suggesting that the former requires active effort (Spence et al. 2004). The functional imaging of memory suppression suggests similar processes (Anderson et al. 2004). To date, however, there has been little functional imaging work on self-deception.Similarly, although evil has always been a key concern of philosophical thought, a cognitive-affective neuroscience of evil has emerged only in recent years (Stein 2000). Evil actions are not homogenous, and this area of research again comprises a number of different strands. First, there are actions where the primary aim is not necessarily to hurt, but where harm is in fact inflicted. (A contested, but perhaps useful example, is the battery-raising of animals for human consumption [Singer 2001]). Second, there are actions where the aim is to hurt, and where harm to the other may even be enjoyed. (During normal altruistic punishment, for example, reward circuitry is activated [de Quervain et al. 2004]). Third, there are actions characterized by impulsive aggression, and a relative absence of executive control. (There may be psychobiological distinctions between reactive aggression in response to frustration or threat, and instrumental aggression that is more goal directed [Blair 2004]).What are the implications of these two sets of cognitive-affective neuroscience literature for a philosophical consideration of evil and of narcissism? [End Page 261] It may be useful to differentiate healthy processes (e.g., having sufficient frontal cortical activity to be able to deceive others) from psychopathologic processes (e.g., not having the necessary frontal-amygdala circuitry required for empathic processing of emotions in social interaction). Similarly, it may be useful to differentiate between normal healthy narcissism (Taylor and Brown 1988) and pathologic malignant narcissism (Kernberg 1985), and between normal altruistic punishment (Hamilton 1963) and pathologic sadistic personality (Kaminer and Stein 2001). In addition, it is perhaps the case that some cognitive-affective processes that do not seem to involve psychopathology may nevertheless be seen as evil (e.g., arguably, the processes that allow a human to eat a battery-raised chicken), whereas some cognitive-affective processes that are clearly psychopathologic may not be viewed as evil (e.g., impulsive aggression in the context of a frontal lobe tumor may be viewed as excusable, as "mad" rather than "bad").Taken together with recent work on the cognitive-affective neuroscience of psychopathy, narcissism, and sadism, these considerations may lead to somewhat different approaches from those taken by Peck and Davidson. In his work on psychopathy, for example, Blair emphasizes a dysfunction in cognitive-affective processing resulting in abnormalities in the weighing up of social emotions (Blair 2004). This account is not inconsistent with a view that in psychopathy there is a disturbance in moral processing that is evil (contra Peck). Furthermore, this... (shrink)

Data are presented that focus on the nature and development of argumentative reasoning. In particular our study describes how support for or against an issue affects memory for critical parts of an argumentative interaction, judgments of argument goodness, and the content of the reasons given in support of one view versus another. Two other factors were examined: developmental differences in argumentation skill and the conditional nature of supporting one side of an argument across varying contexts. Our results show that even (...) seven year old children can recognize, identify, and use the basic components of an argument to provide evidence for and make judgements about their favored position. Moreover, if position support is held constant across all age groups of students, seven year old children were found to give reasons and explanations that were highly similar in content and principle to college students. The same similarities held across age with respect to biases in memory and judgements of argument goodness. The primary difference between children's and college students' argument behavior lay in the side of an argument the students chose to support. Seven year old children and some eleven yearold children supported positions that impute more value to friendship and social consequences than to the maintenance and advancement of individual rights, as specified in a contract agreement. The similarities and differences across development are discussed with respect to a theory of argumentation that speaks to the importance of understanding the nature of goal conflict and a theory of intentionality in predicting how arguments will be represented and resolved. (shrink)

Cell line immortalisation is a growing component of African genomics research and biobanking. However, little is known about the factors influencing consent to cell line creation and immortalisation in African research settings. We contribute to addressing this gap by exploring three questions in a sample of Xhosa participants recruited for a South African psychiatric genomics study: First, what proportion of participants consented to cell line storage? Second, what were predictors of this consent? Third, what questions were raised by participants during (...) this consent process? 760 Xhose people with schizophrenia and 760 controls were matched to sex, age, level of education and recruitment region. We used descriptive statistics to determine the proportion of participants who consented to cell line creation and immortalization. Logistic regression methods were used to examine the predictors of consent. Reflections from study recruiters were elicited and discussed to identify key questions raised by participants about consent. Approximately 40% of participants consented to cell line storage. The recruiter who sought consent was a strong predictor of participant’s consent. Participants recruited from the South African Eastern Cape, and older participants, were more likely to consent; both these groups were more likely to hold traditional Xhosa values. Neither illness nor education were significant predictors of consent. Key questions raised by participants included two broad themes: clarification of what cell immortalisation means, and issues around individual and community benefit. These findings provide guidance on the proportion of participants likely to consent to cell line immortalisation in genomics research in Africa, and reinforce the important and influential role that study recruiters play during seeking of this consent. Our results reinforce the cultural and contextual factors underpinning consent choices, particularly around sharing and reciprocity. Finally, these results provide support for the growing literature challenging the stigmatizing perception that people with severe mental illness are overly vulnerable as a target group for heath research and specifically genomics studies. (shrink)

In this paper we aim to discuss a theoretical explanation for the positive relationship between patients’ knowledge and their trust in healthcare personnel. Our approach is based on John Dewey’s notion of continuity. This notion entails that the individual’s experiences are interpreted as interrelated to each other, and that knowledge is related to future experience, not merely a record of the past. Furthermore, we apply Niklas Luhmann’s theory on trust as a way of reducing complexity and enabling action. Anthony Giddens’ (...) description and analysis of the high modern society provides a frame for discussing the preconditions for patient-healthcare personnel interaction. High modernity is dominated by expert systems and demands trust in these. We conclude that patient knowledge and trust in healthcare personnel is related because both knowledge and trust are future- and action-oriented concepts. The traits of high modernity provides opportunities and challenges as the personnel can and must perform discretion. This discretion must be made in a context where knowledge is considered uncertain and preliminary. (shrink)

This chapter contains sections titled: Philosophical Context Knowing History The Content of History and Historiography Conclusion Further Reading.

The 1953 discovery of the DNA double helix (Watson and Crick 1953) and the elucidation of the molecular basis for inheritance marked the dawn of a new era. When the U.S. Human Genome Project was in...

Both in formal situations (as school teachers, football trainers, etc.) and in many, often unpredictable informal situations (both inside and outside institutions)—adults come close to children. Whether we intend it or not, we continually give them examples of what it is to live as a human being, and thereby we have a pedagogical responsibility. I sketch what it could mean to let ourselves “be built up”, in a Kierkegaardian sense, on the foundation of unconditional love, presupposing that this love is (...) possible for all human beings. Kierkegaard’s Upbuilding discourses invite each reader to engage in a dialogue with the possibilities in the text. Thereby the reader may become aware of his or her present situation in life and see possible alternatives. These discourses or “talks” (taler in Danish) exemplify a manner of indirect communication which perhaps may be transferred to encounters with works of art in general: How could I let examples in literature, pictures, films and music invite and challenge me—to ask myself who I am right now and who I ought to be? My aim is to present an alternative to the instrumental advices that adults are given today. I attempt to clarify the leading concept “upbuilding examples”, sketch the difference between upbuilding, education and Bildung, refer to works of art that seem to have upbuilding possibilities, and consider why upbuilding examples should be studied and how they could be studied in small self-governed groups of adults. (shrink)

In 1856, the State of Ohio began an enumeration of its population to count and identify people with disabilities. This paper examines the ethical role of the accounting profession in this project, which supported the transatlantic eugenics movement and its genocidal attempts to eliminate disabled persons from the population. We use a theoretical approach based on Levinas who argued that the self is generated through engagement with the Other, and that this engagement presupposes a responsibility to and for the Other. (...) We show that successive waves of legislation relied on State and County auditors along with Township clerks and assessors to conduct the mechanics of the enumeration of the population, which focused on the identification, categorization, and counting of the disabled people of the State. We argue that the accounting-based technologies of enumeration and reporting objectify the enumerated persons and deny the auditor’s pre-existing ethical obligation to this new Other. We show how the financial expertise and structures of the State were engaged in the execution of this mandate, which remained in place for over a century and supported a program of institutionalization. We consider the ramifications of this for our understanding of the ethical role of public sector accounting in the United States over this period, which has been under-explored. (shrink)

In the contemporary domain of American legal thought there is a dominant way in which lawyers and judges craft their argumentative practice. More colloquially, this is a dominant conception of what it means to 'think like a lawyer'. Despite the widespread popularity of this conception, it is rarely described in detail or given a name. Justin Desautels-Stein tells the story of how and why this happened, and why it matters. Drawing upon and updating the work of Harvard Law School's (...) first generation of critical legal studies, Desautels-Stein develops what he calls a jurisprudence of style. In doing so, he uncovers the intellectual alliance, first emerging at the end of the nineteenth century and maturing in the last third of the twentieth century, between American pragmatism and liberal legal thought. Applying the tools of legal structuralism and phenomenology to real-world cases in areas of contemporary legal debate, this book develops a practice-oriented understanding of legal thought. (shrink)

The main question on which this essay focuses is: What expectations should a Christian social ethics form concerning a constructive education strategy which can adequately respond to social needs within a globalised world? In order to do so, the first task is to identify the signs of the times: What are the impacts challenging education? What is essentially needed to help secure the necessary requirements for people to live together in a humane and peaceful way under conditions of socio-economic and (...) socio-cultural differences, manifold experiences of alienation, and the potentials for conflict that these bring about? If education as a major means of social participation ought to contribute to this, it must first of all be concerned with the personal identity of young people. The crucial point of education for ‘the citizens of the world’ will be to connect experiences that form identity with the capability to transcend one’s own horizon without fearing the loss of one’s identity. (shrink)

Views of what role convention plays in the creation and appreciation of art works gravitate towards two extremes. One view holds that works of art can be apprehended and appreciated as well as created with no reference to convention. The other claims that conventions fully determine how works of art are apprehended and are therefore necessary conditions for the creation of works of art as well as constitutive of appreciation. The former is a version of the Romantic view of art (...) as something that appeals spontaneously to man's most profound emotions, to man's sentient nature, without making use of or needing mediating conventions. The conventionalist view denies that it is possible to respond spontaneously to art. All apprehension and appreciation of art are structured by conventions, and the reader/audience cannot go beyond these conventions because they constitute the experience of the work of art. This paper explains the sense in which the constitutive view may be best understood. (shrink)

This chapter contains sections titled: Critical Theory's Attack on Biography The Attack from within Literary Criticism Distinguishing a Category of Relevant Biographical Information Biographical Information as an Aid to Understanding Biographical Information as an Aid to Appreciation Biographical Information as an Integral Part of Appreciation Conclusion.

In Euripides' Hippolytus, Phaedra, wife of Theseus, king of Athens, falls in love with the unsuspecting Hippolytus, Theseus' son by the amazon Antiope. Phaedra's passion is the work of the goddess Aphrodite, who wants to revenge herself on Hippolytus because he has rejected her and devoted himself to the chaste Artemis. Through Paedra's nurse Hippolytus is made aware of her love and invited to her bed. He emphatically rejects her offer and violently abuses Phaedra and her nurse. To save her (...) honour Phaedra commits suicide and leaves a note accusing Hippolytus of raping her. Theseus, confronted on his return from an expedition with the suicide and the note, banishes Hippolytus and prays to his father, the seagod Poseidon, to fulfil one of the three wishes he has granted him and kill Hippolytus. Leaving Troezen, Hippolytus is killed when his horses are frightened by a monster thrown on shore by Poseidon from a giant wave. Theseus is brought to realize his mistake by the goddess Artemis who appears to him and reveals the truth. The play ends with the reconciliation of Theseus and the dying Hippolytus. This, in bare outline, is what happens in the play. It is what might be called its subject. The play is about these events and characters. Now it is also possible to give another type of description of Euripides' play. For the play does not merely have a subject but also a theme. While it is straightforward and unproblematic to give a description of the subject of the play a statement of its theme presents difficulties. The subject is, in an obvious sense, given for any competent speaker of the language in which the work is written. The theme, on the other hand, emerges from the subject in conjunction with other features of the work, and it emerges through the reader's constructive labour. There is no theme for the reader who is unwilling or unable to engage in this constructive labour. (shrink)

In Euripides' Hippolytus, Phaedra, wife of Theseus, king of Athens, falls in love with the unsuspecting Hippolytus, Theseus' son by the amazon Antiope. Phaedra's passion is the work of the goddess Aphrodite, who wants to revenge herself on Hippolytus because he has rejected her and devoted himself to the chaste Artemis. Through Paedra's nurse Hippolytus is made aware of her love and invited to her bed. He emphatically rejects her offer and violently abuses Phaedra and her nurse. To save her (...) honour Phaedra commits suicide and leaves a note accusing Hippolytus of raping her. Theseus, confronted on his return from an expedition with the suicide and the note, banishes Hippolytus and prays to his father, the seagod Poseidon, to fulfil one of the three wishes he has granted him and kill Hippolytus. Leaving Troezen, Hippolytus is killed when his horses are frightened by a monster thrown on shore by Poseidon from a giant wave. Theseus is brought to realize his mistake by the goddess Artemis who appears to him and reveals the truth. The play ends with the reconciliation of Theseus and the dying Hippolytus. This, in bare outline, is what happens in the play. It is what might be called its subject. The play is about these events and characters. Now it is also possible to give another type of description of Euripides' play. For the play does not merely have a subject but also a theme. While it is straightforward and unproblematic to give a description of the subject of the play a statement of its theme presents difficulties. The subject is, in an obvious sense, given for any competent speaker of the language in which the work is written. The theme, on the other hand, emerges from the subject in conjunction with other features of the work, and it emerges through the reader's constructive labour. There is no theme for the reader who is unwilling or unable to engage in this constructive labour. (shrink)

This chapter contains sections titled: I II III IV V VI VII.

The exact process that leads to the eruption of autoimmune reactions against β cells and the evolution of diabetes is not fully understood. Macrophages and T cells may launch an initial immune reaction against the pancreatic islets of Langerhans, provoking inflammation and destructive insulitis. The information on the molecular mechanisms of the emergence of β cell injury is controversial and points to possibly important roles for the perforin–granzyme, Fas–Fas-ligand (FasL) and tumor-necrosis-factor-mediated apoptotic pathways. FasL has several unique features that make (...) it a potentially ideal immunomodulatory tool. Most important, FasL is selectively toxic to cytotoxic T cells and less harmful to regulatory T cells. This review discusses the intrinsic sensitivity of β cells to FasL-mediated apoptosis, the conditions that underlie this β cell sensitivity, and the feasibility of using FasL to arrest autoimmunity and prevent islet allograft rejection. In both the autoimmune and transplant settings, it is imperative to progress from the administration of nonspecific immunosuppressive therapy to the concept of β-cell-specific immunomodulation. FasL evolves as a prime candidate for antigen-specific immunomodulation. BioEssays 28: 211–222, 2006. © 2006 Wiley periodicals, Inc. (shrink)

The exact process that leads to the eruption of autoimmune reactions against β cells and the evolution of diabetes is not fully understood. Macrophages and T cells may launch an initial immune reaction against the pancreatic islets of Langerhans, provoking inflammation and destructive insulitis. The information on the molecular mechanisms of the emergence of β cell injury is controversial and points to possibly important roles for the perforin–granzyme, Fas–Fas-ligand (FasL) and tumor-necrosis-factor-mediated apoptotic pathways. FasL has several unique features that make (...) it a potentially ideal immunomodulatory tool. Most important, FasL is selectively toxic to cytotoxic T cells and less harmful to regulatory T cells. This review discusses the intrinsic sensitivity of β cells to FasL-mediated apoptosis, the conditions that underlie this β cell sensitivity, and the feasibility of using FasL to arrest autoimmunity and prevent islet allograft rejection. In both the autoimmune and transplant settings, it is imperative to progress from the administration of nonspecific immunosuppressive therapy to the concept of β-cell-specific immunomodulation. FasL evolves as a prime candidate for antigen-specific immunomodulation. BioEssays 28: 211–222, 2006. © 2006 Wiley periodicals, Inc. (shrink)