bluuebunny/crossref_metadata_2025 huggingface dataset:
Marriage, Mental Handicap, and Sexuality
Authors: Flannery Kevin L.
Published: June 2007

An examination of traditional sources for the Roman Catholic under-standing of marriage reveals that the ends of marriage might be ordered differently, given different contexts. This permits one working within that tradition to see marriage as a political and cultural entity existing independently of the individuals who participate in it. Marriage is also the standard with respect to which sexual activity is judged to be proper or not, a standard that applies to all human beings by virtue of their rational nature. Understanding this allows one to understand how some people, including some of the mentally handicapped, might legitimately be prevented from marrying and even from engaging in genital sexual activity. It also allows one to solve some theoretical difficulties regarding contraception and homosexuality and connected with the fact that sterile couples cannot procreate and yet are permitted to marry.
The Methodist Church’s initiative to use its vacant land to support homeless people’s housing and livelihoods in South Africa
Authors: Bolnick Joel , van Rensburg Greg
Published: June 2007

This paper describes an initiative by the Methodist Church in South Africa to identify vacant land it owns that could be allocated to housing projects for homeless families and, in rural areas, to support their livelihoods. Working with the South African Homeless People’s Federation, this initiative is reviewing Church records, checking them against other official records, and identifying and visiting potential land sites larger than one hectare. This will result in a list of land sites that can be developed by the Church and the Federation. The initiative is also important in encouraging more action from the government on land redistribution and tenure reform, and in setting an example that, hopefully, other Churches will follow.
When utilities muddle through: pro-poor governance in Bangalore’s public water sector
Authors: Connors Genevieve
Published: June 2007

The aim of this paper is to show how messy and slow paths to reform can have useful lessons for public-sector water utilities in developing countries, most of which continue to operate in a climate of muddling through. Using the case of the Bangalore Water Supply and Sewerage Board (BWSSB), this paper analyzes the shifts in policy and operations behind the BWSSB’s innovative work to connect the city’s slum dwellers to the piped water supply. Rather than routinely criticize public utilities for their failure to reach the poor, this paper argues that local successes that start small and are slow to diffuse should be recognized and disseminated across organizations. This is particularly important in the wake of the targets set in the Millennium Development Goals, which run the risk of masking both the importance of how public agencies learn and the factors driving genuine changes in organizational behaviour and urban governance.
Participatory governance in Peru: exercising citizenship
Authors: Hordijk Michaela
Published: June 2007

This paper discusses participatory budgeting as a learning process, with an analysis of two cases of participatory budgeting in Lima, Peru. Peru is the only country in the world where it is legally required that local and provincial authorities should formulate comprehensive development plans and budgets in a participatory manner. The first case discussed is Villa El Salvador, one of the cities that set the example for the framework law on participatory budgeting. The second is the district of San Juan de Miraflores, where municipal officials and inhabitants are currently struggling to implement the new law. This paper suggests that despite obvious shortcomings and a wide variety of implementation problems, the new legal framework offers interesting opportunities for participatory governance.
The role of civil society in urban environmental rehabilitation: a case study (Thanh Xuan district, Hanoi, Vietnam)
Authors: Parenteau René , Thong Nguyen Quoc
Published: June 2007

This paper presents the first results of research on a participatory approach to environmental rehabilitation in Thanh Xuan district in Hanoi, Vietnam, that is part of a larger research project that also included four other case studies. The researchers had two main objectives: first, to identify the civil society actors within a socialist, centralized regime where public participation is quite limited; and second, to assess the role of these actors in performing urban environmental management activities – planning and monitoring, urban environmental services delivery, and urban environmental conflict resolution. Findings from the Thanh Xuan case study suggest that members of the organizations that took part benefited from their participation in the areas of training, empowerment and capacity development. However, the benefits did not seem sustainable, as they were the outcome of international aid and support, and few mechanisms existed to ensure their continuation.
State and civil society in the barrios of Havana, Cuba: the case of Pogolotti
Authors: Ramirez Ronaldo
Published: June 2007

This paper discusses the factors that influenced the success or failure of community projects in one low-income neighbourhood in Havana, Cuba. The scope for community initiatives increased in the late 1980s, in part because of citizens’ desire to take initiatives and collective action to improve their living conditions, in response to the crisis Cuba faced with the disintegration of the communist bloc. The government also allowed civil society more scope, and offered official support to participation and civil society initiatives through Talleres, groups of professionals in the urban and social fields based in each neighbourhood. This paper examines how the people in Pogolotti used available institutions to originate and channel a range of civil society initiatives, including self-help housing construction, a dance group for teenagers, a food conservation project, a children’s musical group, street lighting, forest restoration, recycling and a senior citizens’ house project. It finds that both the state and civil society were positive influences in the origination of successful community projects, which contradicts the assumption that civil-society-initiated projects are more likely to succeed. The state-created Talleres seem to be creating new relationships between civil society and the state; these may be a very small part of Cuban society but they may contain the seeds of new forms of socialist organizations.
Science Fictions
Authors: Squire Corinne
Published: June 2007

This paper argues that reading science fiction can help us understand contemporary debates in feminist psychology and envisage its future. It examines how science fiction, by extrapolating from accepted scientific realities, generates conceptual uncertainties which resemble those existing in feminist psychology around objectivity. The paper then explores how science fiction's stylistic uncertainties are paralleled in feminist psychology. Science fiction's suspensions between science and non-science, literature and non-literature, suggest that interdisciplinarity may be less about dissolving or negotiating disciplinary boundaries, as feminist psychology assumes, and more about contesting or transgressing them. Science fiction also offers feminist psychology valuable models for stylistic rule-breaking, for writing more speculatively and pleasurably, and for operating with two `ends' simultaneously-one extending dominant concepts of gendered subjectivities, the other breaking with them.
Therapy for Lesbians?: The Case Against
Authors: Perkins Rachel
Published: June 2007

From a lesbian feminist perspective the problematic nature of developments in `lesbian' and feminist' psychological therapies is considered. It is argued that such therapies are, despite their expressed aims, essentially anti-lesbian and anti-feminist.
Should `Premenstrual Syndrome' be Called a Psychiatric Abnormality?
Authors: Caplan Paula J. , McCurdy-Myers Joan , Gans Maureen
Published: June 2007

The mental health and political implications of the classification of `Premenstrual Syndrome' (PMS) as a psychiatric disorder are discussed, and the way research in this field is plagued with methodological errors is used to illustrate the power of the political agenda for adopting this deeply flawed and dangerous category.
Technologies and Effects of Heterosexual Coercion
Authors: Gavey Nicola
Published: June 2007

I am concerned here with explicating some of the ways in which sexual coercion, including `unwanted sex', takes place within heterosexual relationships. It is suggested that dominant discourses on heterosexuality position women as relatively passive subjects who are encouraged to comply with sex with men, irrespective of their own sexual desire. Through the operation of disciplinary power, male dominance can be maintained in heterosexual practice often in the absence of direct force or violence. The discursive processes that maintain these sets of power relationships can be thought of as `technologies of heterosexual coercion'. Extracts from women's accounts of their experiences of unwanted and coerced sex with men are presented to show the operations and effects of these technologies of heterosexual coercion.
Against the Dividing of Women: Lesbian Feminism and Heterosexuality
Authors: Thompson Denise
Published: June 2007

I am arguing for a continuity of interests between lesbians and heterosexual women, and that lesbians and heterosexual women have common experiences which enable them to understand and empathize with each other. I document the history of the feminist critique of heterosexuality from early radical feminism to the contemporary arguments of Rich (1980), Raymond (1986) and Penelope (1985a, 1985b, 1985c). From a lesbian feminist standpoint, I suggest that setting up an oppositional dichotomy between `lesbian' and `heterosexual' divides women from each other and perpetuates the heterosexual hegemony. The continuing revaluation and redefinition of lesbianism is essential in order to achieve the political priority of feminism: an end to male domination.
Will the Real Sex Difference Please Stand Up?
Authors: Unger Rhoda K.
Published: June 2007

Scholarship about women and gender in the US is marked by controversies about sex differences; and there is little rapprochement between groups of researchers with different epistemological assumptions. It is argued that empirical investigation of personal epistemology has important implications for feminist scholarship. Following findings of no reliable sex differences in personal epistemology, cross-cultural research showed important interactions between sex and religiosity. This suggests that in order to be able to make statements about the relative importance of sex/gender in predicting behavior, feminist researchers need to subject a wider range of variables to multiple comparisons.
Meeting at the Crossroads: Women's Psychology and Girls' Development
Authors: Brown Lyn Mikel , Gilligan Carol
Published: June 2007

For over a century, psychologists have described adolescence as a time of heightened psychological risk for girls. This article explores a relational impasse or crisis of connection that we have observed in girls' lives at adolescence by tracing through time the thoughts and feelings of two 12-year-old girls who were interviewed as part of a 5-year longitudinal study of girls' psychological development. Using a voice-centered relational method, we join the experiences of struggle and resistance at this developmental juncture with the problems that have been seen as central to the psychology of women.
Foremothers Who Cared: Paula Heimann, Margaret Little and the Female Tradition in Psychoanalysis
Authors: Relke Diana M.A.
Published: June 2007

In 1910, Freud labelled countertransference as pathological, suggesting that analysts either overcome it or quit the profession. It was largely female analysts who, after 40 years of virtual silence on the issue, followed the lead of Paula Heimann and Margaret Little, challenging Freud's anxiety-ridden view and redefining countertransference as an intersubjective mode of relating and a crucial tool of analytic inquiry. This revised view is still questioned by practitioners, many of whom continue to eschew connection and retreat behind Freud's masculine image of the analyst as unemotional and detached. This outmoded analytic ideal hinders contemporary attempts to revise psychoanalysis in feminist terms.
The Mismeasure of Woman
Authors: Tavris Carol
Published: June 2007

Psychology, like society at large, continues to be baffled by the persistent belief that men and women differ in important psychological ways, in spite of countless studies that fail to demonstrate such differences or that capture them for only a brief moment. New approaches avoid the polarization of `male' and female' traits, emphasizing how and why these qualities change over the life span, across cultures and throughout history. To understand where the differences are, we must look to narrative, power, and the conditions of our lives.
Contradictory Positions, Ambivalent Perceptions: A Case Study of a Black Woman Entrepreneur
Authors: Essed Philomena
Published: June 2007

This article addresses black neo-conservatism and the contradictory position of the black middle class in the matrix of domination systems. The empirical basis consists of an open-ended interview with an African-American business woman, an entrepreneur, about her personal success and her role in relation to the black community. The main focus of the article provides an analysis of the arguments she presents to explain problems of race, class, gender and social inequality in society. The resulting picture of beliefs and opinions about inequality and black progress appears to be more complex than a single label like conservatism can account for.
Hungry for an Us: Adolescent Girls and Adult Women Negotiating Territories of Race, Gender, Class and Difference
Authors: Macpherson Pat , Fine Michelle
Published: June 2007

This article explores conversational territory covered by an ongoing `girls' group' of six women, four adults, spanning age, generation, race/ethnicity and social class categories. Discourse analysis of these conversations allows us to follow the young women's collective talk, their early and desperate struggle for sameness, and then to trace our bumpy journey, ultimately, into a discourse of power and difference. The article marvels at our collective ability, among women, to move toward difference, and ends with worries about young women's inability/refusal to analyze for power or difference when talking about `personal' relations with young men.
True or False: The Stratified Self in Lesbian Feminist Theory
Authors: Burack Cynthia
Published: June 2007

Many lesbian feminist philosophers and social theorists have deployed a `false self account' of identity in their work. In this article the implications of this account of the self are identified and critiqued. An alternative relational psychoanalytic account of the self, drawn from the work of D. W. Winnicott, is suggested as useful for the development of lesbian feminist theory.
A Meta/Multi-Discursive Reading of `False Memory Syndrome'
Authors: Schuman Joan , Galvez Mara
Published: June 2007

To understand all the complexities and ramifications of the False Memory Syndrome Foundation's (FMSF) construct of False Memory Syndrome (FMS), we place FMS in the context of larger contemporary western cultural trends, including: anti-feminism; the deconstruction of mental illness; anti-psychiatry; and the postmodern deconstruction of truth and subjectivity. In these contexts, FMSF emerges as an accomplice of the mental health establishment and a leading force in the heteropatriarchal backlash against women.
Sex and Gender Comparisons: Does Null Hypothesis Testing Create a False Dichotomy?
Authors: Favreau Olga Eizner
Published: June 2007

In an ongoing debate about the value of doing tests for sex differences, those in favour claim that if sex differences exist, it is important to know about them. However, the null hypothesis (NH) tests that are used for inferring group differences can detect only mean differences and provide no information about how the differences are distributed across groups. Theoretical and empirical examples show how NH rejection can occur when only a small proportion of individuals differ from all others, demonstrating that these tests are incapable of supporting inferences to general group differences. This forces a reevaluation of sex difference research which has been interpreted as distinguishing males from females in general, particularly where inferences have been to general biological factors. However, even knowing the limitations of these tests may not lead to more judicious interpretations in the context of an androcentric culture which dichotomizes the sexes.
Adopted Women Give Birth: Connection between Women and Matrilineal Continuity
Authors: Hampton Mary Rucklos
Published: June 2007

Twenty women who were adopted as children voice their construction of mothering as they enter the transition to motherhood through giving birth. The tendency for literature on the psychology of adoption to advocate separation between adult mothers and daughters as well as to blame the mothers is challenged by analysing the participants' experiences through a feminist relational paradigm. Daughtering both their adoptive mother-s and birth mothers is an important part of their transition to motherhood. Participants who searched for their birth mothers during this transition were deter-mined to find this mother with whom they had an ongoing, lifelong relationship in order to hear her story. The adopted women in this study constructed a model of matrilineal continuity which defines the mothering and daughtering connection as not limited to a genetic link, but occurring through active, nurturing relationships. They described the importance of their embodied connection with their babies as a way of healing their feelings of separateness as adoptees.
The Impact of Medical and Sexual Politics on Women's Health
Authors: Gannon Linda
Published: June 2007

Hidden agendas impacting women's health care are explored in the context of the intersecting effects of capitalism as the ideology of medical politics, and patriarchy as the ideology of sexual politics. The mutually enhancing forces of medical and sexual politics collide in scientific reductionism - biological determinism for her'. Women are valued according to their ability and willingness to bear and raise children; illnesses and remedies for those women who are unwilling or unable to conform are invented. Thus, the `raging hormones' of puberty and pregnancy tend to be viewed as good and healthy while those associated with the menstrual cycle and menopause are portrayed as unhealthy and in need of alteration. The medical and psychological professions maintain and enhance their power, prestige and profits and serve the patriarchy by labeling events in the normal life course of women as illnesses, reinforcing social misogyny with medical misogyny, emphasizing reproduction rather than health in prioritizing empirical and clinical research, and attributing women's emotions and behaviors to hormonal fluctuations rather than economic, political and social causes.
`It's a Woman's Cry for Help': A Relational Perspective on Postnatal Depression
Authors: Mauthner Natasha S.
Published: June 2007

The two most influential bodies of work on postnatal depression are studies informed by the medical model and feminist analyses. This article begins by reviewing medical and feminist theories, highlighting their contributions to our understanding of postnatal depression as well as their limitations. In particular, clinical studies have focused on the individual mother and her circumstances, while feminist theories have emphasized the sociopolitical context at the expense of the individual. This article argues that a relational approach, which takes `relationship' as a unit of analysis, and explores women's feelings in terms of their relationships to themselves, their interpersonal relationships, and their varying relationships to cultural and structural opportunities and constraints, provides a fruitful way of understanding postnatal depression. The article discusses a qualitative study of 18 women's experiences which aimed to develop such an understanding of postnatal depression. Drawing on feminist and relational methodology and theory, the study sought to explore and prioritize women's own understandings and accounts of their experiences; elucidate the processes through which the women became depressed; and understand postnatal depression in terms of the similarities and differences between the women and their lives.
Joy to the World! A (Healthy) Child Is Born! Reconceptualizing Harm in Wrongful Conception
Authors: Priaulx Nicolette
Published: June 2007

The wrongful conception action holds both a troubled past and future. As a response to rapid technological advancement in the area of reproduction, this action has introduced complex legal and ethical issues in the courts efforts to respond to the question: Can parenthood ever constitute an injury? At the heart of this dilemma lies the manner by which both law and society conceptualize harm is this part of the normal vicissitudes of life or a harmful event? But this question is not decided within a legal vacuum and public policy factors have deeply influenced the nature and existence of case law in this field. In the context of the controversial cases of McFarlane v Tayside Health Board [2000] and Rees v Darlington Memorial Hospital [2002], this article critically examines how harm is judicially characterized and explores the various tensions emerging from conflicting harm constructs. In arguing that the courts must seek to find a balanced approach between public policy concerns and reproductive autonomy, this article will present a fresh theoretical perspective to the conceptualization of harm based on autonomy as the central organizing principle.
Conceptualizing Access to Justice and Victims’ Rights in International Sentencing
Authors: Henham Ralph
Published: June 2007

The purpose of this article is to confront some of the theoretical and conceptual difficulties in understanding the meaning and relevance of notions of access to justice and rights for victims in the context of international sentencing. In particular, it suggests the need for such conceptualizations to engage with the nature of international sentencing process as a transformative mechanism where fact and value are negotiated to correspond with the moral ideologies of the powerful. It is argued that for international penality to progress beyond partisan ideology, rhetorical symbolism and the dynamics of retribution and vindictiveness require us to recognize and understand how moral values and moral action are linked through process and the significance of this for the legitimacy of punishment. For victims and victim communities in international conflict this means conceiving of participation and rights as processual reality and a recognition that any constructive engagement with notions of truth and justice must be grounded in context.
‘We are Family’: The Regulation of ‘Female-Only’ Reproduction
Authors: Lttichau Ingrid
Published: June 2007

In this article I seek to examine the ways in which gay and lesbian struggles are shaped by their political and national context. I have analyzed the public debate concerning assisted insemination in relation to same-sex parenting and single mothers in Denmark as it took place during the years 1997–2002, and, as such, this article offers a reading of sexual politics in a country which is often portrayed as one of the most liberal ones when it comes to gay and lesbian rights. I further show the way in which the rights agenda can prove problematic and limited, in relation to issues of family and parenting. Thus I point to the inherent problems of a universalized conception of gay and lesbian struggles and find it pertinent to consider how organizing frameworks such as gender, sexuality and nationality determine the site of resistance and the articulation of what can be deemed political.
IMF Conditionality as Investment Regulation: A Theoretical Analysis
Authors: Kalderimis Daniel
Published: June 2007

The International Monetary Fund (IMF) was created in 1944 to administer a codified system of fixed exchange rates, and thereby promote a more stable world. In the 1970s, fixed exchange rates were abandoned, leading the IMF to seek new tasks. The IMFs modern role is as a long-term lender to developing countries with chronic balance of payments problems. The IMFs prime tool of influence is conditionality: the provision of credit only where the debtor country meets certain criteria, or enacts certain policies. This article examines the intersection between the IMFs conditionality policies and foreign investment. Although not designed to regulate foreign investment, the IMF has often required capital liberalization as a condition of credit. This article explores the implications of such conditionality and finds it problematic. Investment conditionality is outside the IMFs mandate, difficult to reconcile with existing instruments of investment regulation, inimical to democracy and ineffective at ensuring stable change. These conclusions urge a reconsideration of the governance and operations of the IMF, both in relation to foreign investment, and generally.
Tarrying on the Lord: Affections, Virtues and Theological Ethics in Pentecostal Perspective
Authors: Castelo Daniel
Published: June 2007

As Pentecostals begin to inquire what might constitute Pentecostal theology, the matter must also arise as to what constitutes Pentecostal ethics, both as a matter of logical sequence and as a necessity given the historical and theological links the Pentecostal movement has with the Holiness movement of the nineteenth century. Both areas must be localized in the context of Pentecostal worship, and essential to the field of ethics are the affections and virtues, two moral frameworks that have proven useful for Christian moral reflection. Rather than choosing one or the other, Pentecostals can employ these frameworks in a complementary manner, for each framework has particular accents that are crucial for describing how the moral life takes shape and is sustained. The author employs the activity of ‘tarrying’ from Pentecostal worship as a metaphor for the Pentecostal vision of the moral life in order to show how Pentecostals may continue to embody distinctively their eschatological vision of God at a time when they are negotiating competing allegiances as they emerge as a sub-tradition within Christianity.
The Ideology of Power in Early American Pentecostalism
Authors: Althouse Peter
Published: June 2007

This essay contends that early American Pentecostalism has been shaped and defined by an underlying ideology of power, moulding its charismatic experiences and theological declarations. To demonstrate this, section one will describe how the ideology of power nourished early Pentecostal theology. Section two will offer an interpretive analysis of the social implications of power using the sociological theories of Max Weber and Emile Durkheim. By way of conclusion I suggest that the ideology of power in early Pentecostalism functions as a hermeneutical key.
A comparative trial of imipenem versus ceftazidime in the release of endotoxin and cytokine generation in patients with Gram-negative urosepsis
Authors: Luchi Michael , Morrison David C. , Opal Steven , Yoneda Ken , Slotman Gus , Chambers Henry , Wiesenfeld Harold , Lemke Jon , Ryan John L. , Horn David , Urosepsis Study Group
Published: June 2007

Evidence from in vitro experiments and animal and human studies indicate that antibiotic therapy may induce the release of endotoxin from the outer membrane of Gram-negative bacteria. Antibiotics that bind preferentially to penicillin-binding protein-2 (PBP-2) —such as imipenem — are associated with little release of endotoxin, while antibiotics that preferentially bind to PBP-3 — such as ceftazidime — are associated with far greater release of endotoxin. We conducted a randomized, multicenter, double-blind study comparing imipenem to ceftazidime in patients with urinary tract infections caused by Gram-negative bacilli associated with signs and symptoms of systemic inflammation. A total of 33 patients were randomized to receive either imipenem ( n = 14) or ceftazidime ( n = 19) for initial treatment for urosepsis. No differences in plasma endotoxin, interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α) or urine endotoxin, IL-6 or IL-8 levels were found between the two treatment groups within the first 8 h after antibiotic administration. We conclude that, if differences exist with respect to endotoxin release by these two antimicrobial agents, these differences are not readily demonstrable in this clinical study with carefully defined patients with Gram-negative urinary tract infections.
Limits of a deletion spanning Tlr4 in C57BL/10ScCr mice
Authors: Poltorak Alexander , Smirnova Irina , Clisch Renee , Beutler Bruce
Published: June 2007

Proceeding from our observation that LPS-unresponsive mice of the strain C57BL/10ScCr mice fail to express the Tlr4 gene [Poltorak A, He X. Smirnova I et al. Defective LPS signaling in C3H/HeJ and C57BL/10ScCr mice: mutations in Tlr4 gene. Science 1998; 282: 2085], we have defined the exact limits of a deletion encompassing Tlr4 in the C57BL/10ScCr genome. The deletion removes 74723 bp of DNA, with reference to the control strain 129/J (from which the complete sequence of the Tlr4 locus was obtained). There is no inserted element, and no re-arrangement of the chromosome (e.g. inversion or translocation) in the immediate region of Tlr4; the deletion removes only one recognizable gene. Hence, other immunological anomalies that have been identified in C57BL/10ScCr mice (a non-healing phenotype in Leishmania inoculation and failure to produce interferon-γ in response to numerous microbial infections) must be ascribed to one of two causes. Mutation(s) at other loci may be responsible for these defects. Alternatively, Tlr4 locus deletion may have phenotypic consequences that exceed the well known blockade of LPS signal transduction.
Complement activation by Proteus mirabilis negatively charged lipopolysaccharides
Authors: Kaca Wieslaw , Literacka Elzbieta , Sjóholm Anders G. , Weintraub Andrej
Published: June 2007

Proteus mirabilis strains are human pathogens responsible for urinary tract infections and bacteremias and may be involved in rheumatoid arthritis. Lipopolysaccharide (LPS, bacterial endotoxin), the major component of the cell wall, is one of the virulence factors of Proteus. In the presented studies, we have investigated complement activation by LPSs isolated from P. mirabilis O10, O23, O30, and O43 strains, which differ in the number of negative COO— groups on their polysaccharide components. Four P. mirabilis strains studied were sensitive to complement-mediated killing, despite complement binding by their LPSs. The optimal complement binding by LPSs was detected in serum with functional assays for both the classical and alternative pathways.

Complement activation in 80% serum by the smooth, uronic acid, and hexosamine containing P. mirabilis LPSs was not critically determined by the structure of their O-chain polysaccharides. One of four LPSs used as a model, P. mirabilis O10 LPS, fragmented C3 in an LPS dose- and time-dependent manner. It was detected by crossed-immunoelectrophoresis and capture ELISA with anti-C3c antibodies. The lower complement activation by O23 LPS correlates with its reduced C3 fragmentation, compared with three other Proteus LPSs studied. Rabbit anti-O antibodies enhanced the complement binding and factor C3 fragmentation by O10, O23, O30, and O43 P. mirabilis LPSs.
Review: Lipopolysaccharides in the development of the Guillain-Barré syndrome and Miller Fisher syndrome forms of acute inflammatory peripheral neuropathies
Authors: Prendergast Martina M. , Moran Anthony P.
Published: June 2007

Guillain-Barré syndrome (GBS), an acute inflammatory polyneuropathy, is preceded in most cases by an infectious illness, and Campylobacter jejuni, a leading cause of acute gastroenteritis, is the most common antecedent to GBS and its ocular variant, Miller Fisher syndrome (MFS). O (Penner) serotyping is considered to distinguish between C. jejuni strains based on differences in lipopolysaccharide (LPS) structure. Serotypes of C. jejuni uncommon in enteritis, such as serotype O:19 and O:41, have been associated with GBS. Chemical studies on the core oligosaccharide (OS) of C. jejuni LPSs from serotypes including O:1, O:2, O:4, O:10, O:19, O:23, O:36 and O:41 have revealed structures that mimic human gangliosides including GM1, GD1a, GD 2, GD3, and GM2. Research has focused on the view that molecular mimicry may be a factor in the pathogenesis of GBS. Serum antibodies against gangliosides, particularly GM1 ganglioside, are present in 30% of GBS patients, and are highly associated with MFS, but are generally absent in enteritis cases uncomplicated by neuropathy. Collective data from human and animal studies with anti-ganglioside antibodies suggest a pathogenic role for the antibodies. Many aspects of the pathogenesis of GBS are unclear, in particular how LPS is presented to T cells or the role of host factors in disease development.
A monoclonal antibody recognizing the 3-deoxy-D-manno-oct-2-ulosonic acid (Kdo) trisaccharide αKdo(2→4)αKdo(2→4)αKdo of Chlamydophila spacepsittaci 6BC lipopolysaccharide
Authors: Brade Lore , Rozalski Antoni , Kosma Paul , Brade Helmut
Published: June 2007

A monoclonal antibody (mAb) S45-18 was generated against a synthetic neoglycoconjugate containing the trisaccharide αKdo(2→4)αKdo(2→4)αKdo (Kdo, 3-deoxy-D- manno-oct-2-ulopyranosonic acid) which represents a structure of the lipopolysaccharide (LPS) from Chlamydophila psittaci 6BC. The antibody was characterized by binding and inhibition assays in ELISA using: (i) the immunizing antigen and chemically synthesized derivatives thereof; (ii) chlamydial elementary bodies (EB); and (iii) LPS of Chl. psittaci 6BC and Chlamydia trachomatis L2. The specificity was determined in comparison to that of mAb S25-23 recognizing the αKdo(2→8)αKdo(2→4)αKdo trisaccharide which represents an epitope shared by all species of the family. MAb S45-18 bound to an epitope of the structure αKdo(2→4)αKdo(2→4)αKdo, with lower reactivity with the (2→8)-(2→4)-linked analog. Using chlamydial EB or LPS, mAb S45-18 bound preferentially to LPS and EB of Chl. psittaci. Therefore, Chl. psittaci LPS contains, in addition to the known genus-specific epitope, a species-specific epitope.
The role of Toll-like receptors and MyD88 in innate immune responses
Authors: Akira Shizuo , Hoshino Katsuaki , Kaisho Tsuneyasu
Published: June 2007

Toll-like receptors (TLRs) are phylogenetically conserved receptors that recognize pathogen associated molecular patterns (PAMPS). We previously generated mice lacking TLR2 and TLR4 and showed the differential role of TLR2 and TLR4 in microbial recognition. TLR4 functions as the transmembrane component of the lipopolysaccharide (LPS) receptor, while TLR2 recognizes peptidoglycan from Gram-positive bacteria and lipoprotein. We also generated mice lacking MyD88, an adaptor involved in IL-1R/TLR signalings. The responses to a variety of bacterial components were completely abrogated in MyD88-deficient cells. However, unlike the signaling mediated by other bacterial components such as lipoprotein and bacterial DNA, activation of NF-κB and MAP kinases was induced in response to LPS even in the absence of MyD88, which indicates the existence of a MyD88-independent pathway. We have recently found that the MyD88-independent pathway is involved in LPS-induced maturation of dendritic cells (DCs).
LPS-induced immune response in Drosophila
Authors: Imler Jean-Luc , Tauszig Servane , Jouanguy Emmanuelle , Forestier Claire , Hoffmann Jules A.
Published: June 2007

The study of the regulation of the inducible synthesis of antimicrobial peptides in Drosophila melanogaster has established this insect as a powerful model in which to study innate immunity. In particular, the molecular characterization of the regulatory pathway controlling the antifungal peptide drosomycin has revealed the importance of Toll receptors in innate immunity. We report here that injection of LPS into flies induces an immune response, suggesting that LPS receptors are used in Drosophila to detect Gram-negative bacteria infection. We have identified in the recently sequenced genome of Drosophila eight genes coding for Toll-like receptors in addition to Toll, which may function as LPS receptors. However, overexpression of a selection of these genes in tissue-culture cells does not result in up-regulation of the antibacterial peptide genes. These results are discussed in light of the recent data from genetic screens aimed at identifying the genes controlling the antibacterial response in Drosophila.
Clinically-oriented therapies in sepsis: a review
Authors: Dubois Marc-Jacques , Vincent Jean-Louis
Published: June 2007

Our insight of the sepsis response has evolved to encompass not only the pro-inflammatory but also an anti-inflammatory reaction following infection. Clinical trials have been designed to target either bacterial products, endotoxin in particular, or mediators involved in the sepsis response, but until recently the majority of them have given unfavorable results. In this article, we provide a scope of clinical trials that have been done in immunomodulation during sepsis whether or not they provide positive results. We will also discuss some of the reasons why those studies have been disappointing. Current and future trials with a better assessment of inflammatory status of patients and better-defined outcomes such as organ dysfunction are now underway.
MALP-2, a Mycoplasma lipopeptide with classical endotoxic properties: end of an era of LPS monopoly?
Authors: Galanos C. , Gumenscheimer M. , Mühlradt P.F. , Jirillo E. , Freudenberg M.A.
Published: June 2007

Although some activities of LPS are shared by other bacterial components, for half a century LPS has been regarded as unique in displaying many pathophysiological activities. Here we report on a synthetic lipopeptide, MALP-2 from Mycoplasma fermentans , which expresses potent endotoxin-like activity and whose lethal toxicity is comparable to that of LPS. With the exception of the Limulus lysate gelation test, in which MALP-2 was approximately 1000-fold less active than LPS, the synthetic lipopeptide induced all activities tested for, and in most cases to an extent comparable to that of LPS. Unlike LPS, the biological activities of MALP-2 were expressed both in LPSresponder and in LPS-non-responder mice (BALB/c/l, C57BL10/ScCr), indicating that MALP-2 signaling, unlike that of LPS, is not transduced via the Toll-like receptor (Tlr) 4 protein. MALP-2 expressed no toxicity in normal or sensitized Tlr2 knockout (Tlr2— /—) mice indicating that its toxic activity is induced via Tlr2 signaling. The phenomenology of the lethal shock induced by MALP-2 in normal or sensitized mice, i.e. the kinetics of its development and symptoms of illness exhibited by the treated animals, was very reminiscent of the lethal shock induced by LPS.
Outer membrane protein A (OmpA), peptidoglycan-associated lipoprotein (PAL), and murein lipoprotein (MLP) are released in experimental Gram-negative sepsis
Authors: Hellman Judith , Shaw Warren H.
Published: June 2007

We previously showed that Escherichia coli bacteria incubated in normal human serum release complexes that contain three conserved Gram-negative bacterial outer membrane proteins (OMPs) and LPS. We have identified the OMPs as outer membrane protein A (OmpA), peptidoglycan-associated lipoprotein (PAL), and murein lipoprotein (MLP). These OMPs are conserved among enteric Gram-negative bacteria and are bound by IgG in antisera raised to heat-killed rough bacteria such as E. coli J5 (J5 IgG). The present experiments were performed to further analyze the release of these OMPs in a rat wound infection model of sepsis. Plasma was collected from thermally injured rats with E. coli O18 sepsis and filtered. LPS was affinity-purified from plasma filtrates using monoclonal antibody specific for the O-polysaccharide side chain of E. coli O18 LPS. Plasma filtrates were also incubated with J5 IgG conjugated to magnetic beads. Affinity-purified samples were analyzed for the OMPs by immunoblotting. OmpA, PAL, and MLP were released into septic rat blood in complexes with LPS. PAL was consistently present in samples affinity-purified using J5 IgG. The results indicate that OmpA, PAL, and MLP are released and circulate in experimental Gram-negative sepsis and suggest that a proportion of released OMPs are tightly associated with LPS.
Invited review: Lipopolysaccharide biosynthesis: which steps do bacteria need to survive?
Authors: Gronow Sabine , Brade Helmut
Published: June 2007

A detailed knowledge of LPS biosynthesis is of the utmost importance in understanding the function of the outer membrane of Gram-negative bacteria. The regulation of LPS biosynthesis affects many more compartments of the bacterial cell than the outer membrane and thus contributes to the understanding of the physiology of Gram-negative bacteria in general, on the basis of which only mechanisms of virulence and antibiotic resistance can be studied to find new targets for antibacterial treatment. The study of LPS biosynthesis is also an excellent example to demonstrate the limitations of `genomics' and `proteomics', since secondary gene products can be studied only by the combined tools of molecular genetics, enzymology and analytical structural biochemistry. Thus, the door to the field of `glycomics' is opened.
Cloning, sequencing, and functional analysis of three glycosyltransferases involved in the biosynthesis of the inner core region of Klebsiella pneumoniae lipopolysaccharide
Authors: Noah Christian , Brabetz Werner , Gronow Sabine , Brade Helmut
Published: June 2007

The genes encoding the 3-deoxy-D- manno-oct-2-ulosonic acid (Kdo) transferase ( waaA) and heptosyltransferases I ( waaC) and II ( waaF) in Klebsiella pneumoniae were cloned from a DNA library by functional complementation of corresponding Escherichia coli and Salmonella enterica mutants. Sequence analyses revealed extensive homologies of the deduced proteins to their counterparts in other Enterobacteriaceae. However, differences were evident with regard to the chromosomal organization of the genes. To perform in vitro studies, the waaA, waaC and waaF genes were subcloned and expressed in the Gram-positive host Corynebacterium glutamicum. WaaA was characterized as a bifunctional enzyme capable of transferring two Kdo residues to a synthetic bisphosphorylated tetraacyl-lipid A precursor of E. coli (compound 406). In contrast, waaC and waaF were shown to encode specific glycosyltransferases catalyzing the consecutive transfer of two L- glycero-D- manno-heptose residues to Kdo2-406.
The involvement of Ran GTPase in lipopolysaccharide endotoxin-induced responses
Authors: Fangping Zhao  , Quan Yuan  , Sultzer Barnet M. , Chung Siu-Wah , Wong Peter M.C.
Published: June 2007

By functional cloning, we have established that Ran GTPase is involved in LPS-induced signal transduction. This has been accomplished by several functional comparisons of the two cDNAs, Lpsn/Ran (or RanT/n) and Lpsd/Ran (or RanC/d), which were isolated from cDNA libraries of LPS responder and hyporesponder mice, respectively. The letter n refers to the `normal' phenotype and the letter d refers to the `deficient' phenotype. Consistent with our previous results, more animal studies indicated that adenoviral transduction of RanC/d cDNA, but not RanT/n cDNA, into sensitive mice conferred significant resistance against endotoxin challenge. Thus the incorporation of RanC/d cDNA into gene therapy protocols as a therapeutic sequence remains very attractive. At steady state, hematopoietic cells transduced with RanC/d cDNA led to about a 10-fold increase in exogenous Ran protein compared with RanT/n cDNA. Furthermore, our cumulative data suggest that a slight elevation of Ran protein in B cells enhances LPS responsiveness, but the same elevation of Ran in macrophages does not. On the other hand, a high level of overexpression of Ran in both macrophages and B cells down-regulates LPS signal transduction. Thus LPS-induced signal transduction in macrophages and B cells is likely to occur via different signaling pathways.
Bacterial modification of LPS and resistance to antimicrobial peptides
Authors: Gunn John S.
Published: June 2007

Antimicrobial peptides (APs) are ubiquitous in nature and are thought to kill micro-organisms by affecting membrane integrity. These positively charged peptides interact with negative charges in the LPS of Gram-negative bacteria. A common mechanism of resistance to AP killing is LPS modification. These modifications include fatty acid additions, phosphoethanolamine (PEtN) addition to the core and lipid A regions, 4-amino-4-deoxy-L-arabinose (Ara4N) addition to the core and lipid A regions, acetylation of the O-antigen, and possibly hydroxylation of fatty acids. In Salmonella typhimurium, LPS modifications are induced within host tissues by the two-component regulatory systems PhoPQ and PmrAB. PmrAB activation results in AP resistance by Ara4N addition to lipid A through the activation of at least 8 genes, 7 of which are transcribed as an operon. Loss of this operon and, therefore, Ara4N LPS modification, affects S. typhimurium virulence when administered orally. Transposon mutagenesis of Proteus mirabilis also suggests that LPS modifications affect AP resistance and virulence phenotypes. Therefore, LPS modification in Gram-negative bacteria plays a significant role during infection in resistance to host antimicrobial factors, avoidance of immune system recognition, and maintenance of virulence phenotypes.
A K+ channel is involved in LPS signaling
Authors: Seydel U. , Scheel O. , Müller M. , Brandenburg K. , Blunck R.
Published: June 2007

We previously showed a clear correlation between the molecular conformation of the lipid A moiety of endotoxin molecules and their cytokine-inducing capacity in mononuclear cells. While conically shaped lipid A moieties exhibit a high agonistic activity, a shift to a more cylindrically shaped lipid A leads to a decrease in agonistic and increase in antagonistic activity of the endotoxin molecules. Here, we show the involvement of a high-conductance Ca2+-activated potassium (MaxiK) channel in LPS signaling in macrophages. Corresponding to their biological activity, endotoxins activate a MaxiK channel as shown in outside-out patch-clamp experiments. LPS antagonists and anti-CD14 antibodies inhibit the LPS-induced activation of the channel. Blocking of the channel by specific channel blockers in macrophage cultures leads to inhibition of cytokine mRNA production. In particular, this result implies that there is no other independent transmembrane signaling pathway operative in macrophages. A shift of the molecular conformation of an a priori antagonistic lipid A from a cylindrical to a conical shape by adding the membrane-active compound chlorpromazine increases the activity of the MaxiK channel and the biological activity of the lipid A. We conclude that the activation of the MaxiK channel is a very early step in LPS-induced signaling in macrophages.