bluuebunny/crossref_metadata_2025 huggingface dataset:
Experience, Identities and Alliances: Jewish Feminism and Feminist Psychology
Authors: Burman Erica
Published: June 2007

This article develops a theoretical perspective on identities as relational and produced through histories of oppression and resistance. The arguments are applied to their expression in issues for feminists teaching psychology and feminists organizing around psychology. As an illustration of key questions around the construction of counter-histories and self-representations, I focus on the changing forms and expressions of Jewish feminism in Britain. The analysis of Jewish identifications draws on recent calls to interrogate the notion of whiteness, and fracture the hegemony of racialization by attending to `different degrees of othering'. This is developed in relation to the possibilities of, and obstacles to, alliances between Jewish and black feminists. In order to document a counter-history, I present an analysis of the presences and absences of Jewish feminist representations, particularly in relation to factors contributing to the non-publication of a British Jewish Feminist Anthology. The article finishes with a reminder of the wider political arenas in which discussions of identity, agency and collective action become increasingly urgent.
Women's Sex Talk and Men's Sex Talk: Different Worlds
Authors: Crawford June , Kippax Susan , Waldby Catherine
Published: June 2007

Communication in heterosexual encounters is often problematic, particularly front the perspective of the woman involved. In examining what renders such communication problematic, this article argues that both hegemonic discourses and particular interpersonal contexts need to be taken into account. Communication and negotiation take place in the intersubjective realm, the space where human beings make sense of their experience. An analysis of memories and accounts provided by groups of men and of women shows how the shared meanings which emerge within such encounters (occasioned meanings) are produced with reference to the dominant discourses. Since these discourses are designed to articulate men's interests, the question of gendered intersubjectivity is particularly salient. Intersubjectivity and negotiation are seen to be related in complex ways. Examples are given of occasions when intersubjectivity is either lacking or incomplete, and it is shown that the male sex drive discourse is one which is then often drawn upon in determining what takes place. This is particularly so for the sexually inexperienced, and thus from a feminist perspective a new discourse of heterosexuality becomes essential.
Blaming Our Mothers, Blaming Ourselves: Women's Accounts of Childhood Abuse and Disruption
Authors: Croghan Rosaleen , Miell Dorothy
Published: June 2007

This article examines the ways in which women who have suffered childhood abuse or disruption explain the breakdown in their relationship with their parents, and the extent to which their attributions of responsibility are influenced by expectations of `normal' parenting and family life. The women `s accounts are analysed in terms of the attributions of responsibility which women make for the disruption in their relations/zips, and the factors which they see as valid in mitigating maternal and paternal responsibility. It is argued that in attempting to come to terms with their experiences the women draw heavily on constructions of parenting and family life which represent the normal family as a private haven in which heterosexual relationships are viewed as both natural and unproblematic and in which women assume primary responsibility for the well-being of the family. It is also argued that this representation of family life leads women to blame and to distance themselves from their mothers, and thus leaves them unable to come to terms with their own disadvantage as women.
Rational Men and Conciliatory Women: Graduate Psychologists Construct Accounts of Argument
Authors: Mapstone Elizabeth
Published: June 2007

Graduate psychologists engaged in research (10 women, 10 men) were interviewed about their recall of and views on argument, defined as `a discursive disagreement between two people, each of whom wishes to convince the other of the validity of her/his point of view'. While most of the men talked of argument as bargaining and debate, all the women expressed concern about the effect of disagreement on relationships. Though this might be interpreted as supporting Gilligan's (1982) `different voice' theory, accounts of arguments vary depending on relationships. Women report difficulties of communication in intimate relationships, but claim success due to logic and rationality in argument with male colleagues and supervisors. By contrast, men report successful communication with close friends, but lack of success with colleagues, and invoke stereotypes when arguments fail with women in all relationships.
Feminist Identifications in a Troubled Society
Authors: Percy Carol , Kremer John
Published: June 2007

This article reports selected findings from a programme of postgraduate research which examined women's identifications with feminism in Northern Ireland. This qualitative study used repertory grids and semi-structured interviews to explore the meanings of feminism with a total of 31 women. It shows how women `s perceptions of feminists have affected their decisions about whether or not to identify themselves as such. The data reported here are from case studies of 26 women. The repertory grids uncovered perceived commonalities and differences between women `s present and ideal selves and feminists, while the interviews revealed some of the conflicts women negotiate in their daily lives and the compromises they must make in attempts at conflict resolution. A conflicting picture emerges in which many women support feminist ideals but do not identify as feminists because of a negative stereotype of feminists. While this stereotype has specific connotations in the context of Northern Ireland, it seems likely that certain aspects of it, and the ways in which it is used, may apply to other patriarchal and heterosexist societies.
`I'm Just a Girl Who Can't Say "No"': A Gender Difference in Children's Perception of Refusals
Authors: Leonard Rosemary
Published: June 2007

An understanding of children's interpretation of refusal statements is an important element in understanding the way girls are encouraged to cooperate with their own oppression. Refusing is a particularly important survival skill for girls growing up in a patriarchal society where boys are trained to be active but girls are trained to be compliant. In each of three samples (N = 27; N = 36; N = 20), girls differed from boys in their identification of a simple `No' as the refusal most likely to annoy an adult. Three possible explanations were explored: compared with boys, girls are less defiant; girls are more advanced; and that their perceptions are accurate. Support was found for the third explanation only. These results are discussed in terms of their implications for reassessing the role of refusals to resolve some of the contradictions around expectations of obedience and assertiveness, while recognizing the interests which benefit from keeping girls and women obedient.
Corpses, Lepers, and Menstruating Women: Tradition, Transition, and the Sociology of Knowledge
Authors: Datan Nancy
Published: June 2007

A study of 1148 middle-aged women in five Israeli subcultures ranging from modern Central European immigrants to traditional Moslem Arab villagers is the point of departure for this essay on tradition, transition and the sociology of knowledge. The study is shown as having evolved through the competing hypotheses of the investigators, which in turn reflect the biases born of the experiential framework: two men and one young woman design a study that assumes an overvaluation of fertility and childbearing. When the findings reveal that middle-aged women do not regret the loss of fertility, regardless of tradition or modernity (and thus of childbearing history), the investigators discover their own assumptions to be erroneous. Further, the meaning of modernity is reconsidered as tradition is shown to incorporate a recognition of the strength of women despite formal status subordination; it is proposed that the dilemma of middle age is inevitably cultural transition. Finally, it is suggested that the broader social context of which the investigators were a part legitimates the study of women as `other' and as objects, while denying opportunity to study men in the same framework-a social context in which men shape decisions that grant or deny research funds, and thus shape the evolution of knowledge of gender.
The Political is Personal: Father-Daughter Relationships and Working-Class Consciousness
Authors: Brewer Sandy
Published: June 2007

This article asks if the 1970s women's liberation slogan `the personal is political' has privileged a `psychologized', that is an individualistic, version of feminism which, being implicitly grounded in middle-class experiences and concerns, has made invisible those of working-class women. It looks at the problems encountered in trying to use psychology to explain reciprocal-as opposed to individual-concerns and psychoanalysis to explore working-class girls' entry into gendered identity. In doing so, the discussion draws upon Jessica Benjamin's work on cross-gender identification to explore the difficulties faced by daughters who learned from an early age of the relative powerlessness of their fathers. It argues that such experiences can be seen not as instances of individual pathologies, but as examples of how early consciousness of class positioning might provide the roots of women's adult political activity which is founded not on a gendered but on a classed identity.
Bloody Women: A Discourse Analysis of Amenorrhea as a Symptom of Anorexia Nervosa
Authors: Malson Helen , Ussher Jane M.
Published: June 2007

Amenorhea, the absence of menstruation, is now considered to be a major diagnostic symptom of anorexia nervosa and has been interpreted as `psychobiological' retreat from adult womanhood. However, such interpretations may be overly simplistic. This article draws on poststructuralist theory to examine the ways in which menstruation and amenorrhea are discursively constituted in relation to constructions of femininity. It is based on interviews with 23 women (21 who had been diagnosed as anorexic and two who were self-diagnosed). Discourse analysis of the interviews indicated that `menstruation' was negatively construed as a signifier of `femininity'. However, it signified a very specific `femininity' that was alien, out of control, highly emotional, sexual, vulnerable and dangerous. It is argued that amenorrhea in anorexia may signify a rejection of this particular negative construction of femininity' rather than of adulthood or femininity per se.
Discourses of Emotionality in Commercial Sex: The Missing Client Voice
Authors: Plumridge Elizabeth W. , Chetwynd S. Jane , Reed Anna , Gifford Sandra J.
Published: June 2007

This paper analyses the discourse of a group of men who buy sex from women, examining the way they explain and justify their pleasure in such sex. They do so through two sets of interpretations: on the one hand they assert that the commercial exchange is a mutual emotional and sexual relationship between clients and the women who provide sex, and on the other hand they assert that the payment of money discharges all larger obligations associated with relationships. The result is a profoundly self-serving interpretative schema in which women who provide sex are ascribed an identity and agency to position clients in an almost wholly benign light.
Materializing the Hypothalamus: A Performative Account of the `Gay Brain'
Authors: Hegarty Peter
Published: June 2007

Simon LeVay's research on neuroscience and sexuality has been reiterated in popular media, scientific communities and legal debates. A close reading of this work, drawing on performativity theory (Butler, 1990, 1993), reveals that this popular success is the result of citing and reiterating a number of heterosexist, sexist and culturally imperialist norms. LeVay's work excludes women and ethnic minorities and denies the political, cultural and historical nature of sexuality. Performativity theory suggests the limits of empiricism for feminists, and the importance of postmodern readings of the subject of psychology and neuroscience.
Political Tolerance among Adolescents towards Feminists
Authors: Sotelo María José
Published: June 2007

This article studies the willingness that adolescents have to extend human rights to feminists. This willingness defines the concept of `political tolerance' towards feminists. The results of this study show that the rights that adolescents are least willing to extend to feminists are those more related to the most visible feminist activities, such as the right of demonstrating on the street. Self-esteem, political experience and identification with a group of friends are positively related to political tolerance towards feminists, whereas support for violent groups or identification with the Catholic Church, and identification with other religious groups are negatively related.
Fantasy, Memory and Reality: Psychoanalytic and Legal Perspectives on Rape
Authors: Burns Linda
Published: June 2007

Feminists have accused psychoanalysis of ignoring the realities of rape and of concentrating instead on fantasy and seduction. John Forrester argues that these accusations rest on a failure to distinguish psychoanalytic discourses from legal ones. Freud's insight into psychic realities and traumatic memories can explain the tendency of many victims of rape to feel guilt and doubt about what occurred. I argue that Forrester misses the point of feminist criticisms of psychoanalysis. His construal of the response of rape victims as retrospective consent conflicts with empirical studies of rape victims. It also rests on an inadequate moral psychology.
Troubled Men and Threatening Women: The Construction of `Crisis' in Male Mental Health
Authors: Coyle Adrian , Morgan-Sykes Caroline
Published: June 2007

In recent years, the development of an apparent `crisis' in male well-being (and, more specifically, in male mental health) has become a focus of media and academic interest. This crisis has been linked to disruptions in the traditional system of gender relations, with men being problematically positioned within a changed social context, especially in relation to issues of emotion. In this study, articles on men's health in a British broadsheet newspaper are subjected to discourse analysis to examine the ways in which the crisis in male mental health has been rhetorically constructed. The analysis suggests that it is constructed as arising from the enactment of a traditional, hegemonic masculinity (seen as militating against emotional expression), gender role changes in the employment and sexual domains and the advance of women. Despite an apparent acknowledgement of a need for change, alternative enactments of masculinity are undermined. The implications of these analyses are explored.
Working with Women in Special Hospitals
Authors: Williams Jennie , Liebling Helen , Lovelock Caroline , Chipchase Hazel , Herbert Yvonne
Published: June 2007

This is an edited version of a conversation that took place between myself and four other clinical psychologists who had been actively involved in developing better services for women living in Ashworth and Rampton hospitals - two of the three high security psychiatric hospitals in England. There have been long-standing concerns about the quality of the services provided by these Special Hospitals,1 and a public inquiry2 in 1992 identified services to women as a particular cause for concern. This inquiry was followed by a period of optimism during which time these psychologists had worked hard to improve services to women in the Special Hospitals. We met in late 1996 to talk about their frustrations and disappointments, to learn from their experiences, and to remember the women who live in these hospitals. This was not an easy conversation, and it was also limited by a pending tribunal and the ever present threat of legal action. The Special Hospitals have continued to feature in news headlines, and their future is being publicly debated. We want this debate to be informed by an understanding of the ways in which Special Hospitals continue to fail women. There is nothing to suggest that they provide women with what they need, or that they are likely to do so in the future. The development of better community mental health services is the only way forward.
Prostitution in Five Countries: Violence and Post-Traumatic Stress Disorder
Authors: Farley Melissa , Baral Isin , Kiremire Merab , Sezgin Ufuk
Published: June 2007

We initiated this research in order to address some of the issues that have arisen in discussions about the nature of prostitution. In particular: is prostitution just a job or is it a violation of human rights? From the authors' perspective, prostitution is an act of violence against women; it is an act which is intrinsically traumatizing to the person being prostituted. We interviewed 475 people (including women, men and the transgendered) currently and recently prostituted in five countries (South Africa, Thailand, Turkey, USA, Zambia). In response to questionnaires which inquired about current and lifetime history of physical and sexual violence, what was needed in order to leave prostitution and current symptoms of post-traumatic stress disorder (PTSD) we found that violence marked the lives of these prostituted people. Across countries, 73 percent reported physical assault in prostitution, 62 percent reported having been raped since entering prostitution, 67 percent met criteria for a diagnosis of PTSD. On average, 92 percent stated that they wanted to leave prostitution. We investigated effects of race, and whether the person was prostituted on the street or in a brothel. Despite limitations of sample selection, these findings suggest that the harm of prostitution is not culture-bound. Prostitution is discussed as violence and human rights violation.
The More the Merrier? A New Take on Legal Pluralism
Authors: Melissaris Emmanuel
Published: June 2007

Legal pluralism provides an alternative and very useful way of thinking about the legal as well as about discourses about the legal, as it sets itself the multiple task of looking at the law and theory both from an internal and an external point of view. This article distinguishes between two main theoretical strands of legal pluralism. Empiricism-positivism includes early sociological endeavours that trace selfregulating social groups and point out that the formal law of the state is not and cannot be responsive enough to those legal orders. Anthropological legal pluralism, which studies the ways peoples living within a congruent State regulate themselves despite the existence of a central law, also belongs here. Empiricism-positivism commits the fallacy of trying to define the law criterially, thus importing in that pluralistic law the knowledge of a dominant legality. This is what the ‘other’ legal pluralism is anxious to avoid. It turns to new ways of understanding the legal and seeks to make sense of and also facilitate the interpenetration of dispersed legalities. In particular, I refer to the work of three theorists. Günther Teubner and his systemstheoretical legal pluralism, Boaventura de Sousa Santos and his suggestion that new subjectivities emerge, and Robert Cover and his account of jurisgenerative commitments and the violence committed by state law. I argue that, although they too suffer from various shortcomings, these three approaches to legal pluralism can be fruitfully combined. From that combination a new understanding of legal pluralism will emerge as the radicalization of the way we think about the legal, an understanding that collapses observation into participation and thus leaves it up to regulatory discourses themselves to organize their communication. Finally, I argue that this legal pluralistic knowledge cannot be achieved by an already established and institutionalized legal order. At a first stage it is academic legal studies that must provide a forum, in which the dispersed legal discourses and theories can reveal themselves and communicate with each other.
Breath from Nowhere: The Silent ‘Foundation’ of Human Rights
Authors: Perrin Colin
Published: June 2007

One is ‘with’ another who is dying. What can one do? What can one say? This article considers the claim that in this insurmountable difference, this insurpassable distance, one cannot be just; one could never say the right thing. In a contribution to ongoing debate about the foundation of human rights, what follows draws upon the work of Jacques Derrida and Maurice Blanchot to argue that an obligation to respond, rather than a reason not to respond, may be derived from this situation. This argument is pursued viaa consideration of the work of Amnesty International and it is outlined here in support of an understanding of human rights as ‘founded’ upon something other than a naÔve faith in ‘human’ commonality and in the possibility of its representation. Taking up this non-response, such an argument turns upon the undecidable difference between a silence that signifies the inexpressibility of one’s concern for the other and a ‘silence’ that ‘expresses’ no concern at all. And the claim here is that a ‘foundation’ for human rights may be traced to the impossibility of being able to tellthis difference; a difference which must therefore be, or must already have been, made.
Endotoxin-induced alterations of lipid and fatty acid compositions in rat liver peroxisomes
Authors: Khan Mushfiquddin , Contreras Miguel , Singh Inderjit
Published: June 2007

The structure/function of peroxisomal lipids in rat liver treated with a sublethal dose of endotoxin, a lipopolysaccharide (LPS), was investigated. Peroxisomes isolated from LPS-treated rat liver had remarkable alterations in lipid content compared with saline treated control liver peroxisomes. Cholesterol and phospholipids (PL) decreased significantly by 28.7% and 50.8%, respectively, leading to the change in the ratio of cholesterol/phospholipids (control 0.081 versus LPS 0.118, P <0.001). A quantitative analysis from LPS-treated rat liver peroxisomes showed a general decrease in all classes of PL. No such alterations were observed in lipid content of other subcellular organelles. The peroxisomal fatty acid composition in LPS-treated animals was also altered. An analysis of fatty acid composition in PL and phosphatidylcholine from LPS-treated peroxisomes showed an increase in arachidonic acid (C20:4) and docosahexaenoic acid (C22:6). Very long chain (VLC) fatty acids (>C22:0) were also found increased in all classes of lipids in LPS-treated peroxisomes. Gadolinium chloride (GAD) mediated inactivation of Kupffer cells (KC) normalized cholesterol/PL ratio in LPS-treated peroxisomes. Collectively, the results indicate that the peroxisome metabolism of lipids and fatty acids is specifically altered in endotoxin-treated rat liver and at least part of the alterations may be mediated by factors released by KC.
The role of polar and facial amphipathic character in determining lipopolysaccharide-binding properties in synthetic cationic peptides
Authors: David Sunil A. , Awasthi Satish K. , Balaram P.
Published: June 2007

Two series of peptides, designated K and NK were synthesized and tested for lipid A binding and neutralizing properties. K2, which has an 11-residue amphiphilic core, and a branched N-terminus bearing two branched lysinyl residues does not bind lipid A, while NK2, also with an 11-residue amphiphilic core comprised entirely of non-ionizable residues, and a similarly branched, cationic N-terminus, binds lipid A very weakly. Both peptides do not inhibit lipopolysaccharide (LPS) activity in the Limulus assay, nor do they inhibit LPS-induced TNF-α and NO production in J774 cells. These results are entirely unlike a homologous peptide with an exclusively hydrophobic core whose LPS-binding and neutralizing properties are very similar to that of polymyxin B [David SA, Awasthi SK, Wiese A et al. Characterization of the interactions of a polycationic, amphiphilic, terminally branched oligopeptide with lipid A and lipopolysaccharide from the deep rough mutant of Salmonella minnesota . J Endotoxin Res 1996; 3: 369—379]. These data suggest that a clear segregation of charged and apolar domains is crucial in molecules designed for purposes of LPS sequestration and that head-tail (polar) orientation of the cationic/hydrophobic regions is preferable to molecules with mixed or facial cationic/amphipathic character.
Signaling pathways involved in lipopolysaccharide stimulation of prostaglandin production by rat hypothalamic astroglial cells
Authors: Pistritto Giuseppa , Ciabattoni Giovanni , Mancuso Cesare , Tringali Giuseppe , Preziosi Paolo , Navarra Pierluigi
Published: June 2007

The aim of this study was to investigate the mechanisms through which bacterial lipopolysaccharide (LPS) stimulates prostaglandin (PG) production in rat hypothalamic astroglial cells in vitro. The latter were treated with LPS alone or LPS plus antagonists of the interleukin-1 (IL-1) and nitric oxide (NO) pathways, and the subsequent changes in cyclooxygenase (COX) activity were monitored by measuring a COX end-product, prostaglandin E2 (PGE2), released into the incubation medium. LPS produced a concentration-dependent increase in PGE2 release from astroglia after 24 h incubation; experiments with selective antagonists showed that the increase in PGE 2 release induced by LPS may be, at least in part, mediated by IL-1 and NO.
Time-dependent effect of LPS on PGE2 and TNF-α production by rat glial brain culture: influence of COX and cytokine inhibitors
Authors: Shemi D. , Azab A.N. , Kaplanski J.
Published: June 2007

This study was undertaken to investigate the effect of lipopolysaccharide (LPS) stimulation on the time course of prostaglandin E2 (PGE) and tumor necrosis factor alpha (TNF-α) production by rat glial brain culture. A concentration of 210 µg/ml LPS from Escherichia coli was used as stimulation treatment. The effect of pentoxifylline (PXF), nimesulide (NIM), indomethacin (INDO) and dexamethasone (DEX) on the regulation of PGE2 and TNF-α production was tested. Stimulation of rat glial cells with LPS resulted in different time-dependent production patterns of PGE2 and TNFα. The time course of TNF-α elevation was short, reaching its peak at 6 h post LPS and decreasing to undetectable levels after 24 h. On the other hand, the time course of PGE2 elevation was longer, starting at 6 h post LPS treatment and increasing 100-fold compared with basal levels, 24 h post LPS exposure. The COX inhibitors (NIM and INDO) and DEX were found to inhibit the LPS-induced elevation in PGE2 production, while PXF lacked such an inhibitory effect. Furthermore, NIM, DEX and PXF were found to reduce the LPS-induced elevation in TNF-α levels, while INDO caused a greater elevation in TNF-α levels. These results may cast further light on the LPS-induced production of PGE2 and TNF-α by rat glial cell cultures and the relation between the two systems.
Co-operative induction of pro-inflammatory signaling by Toll-like receptors
Authors: Ozinsky A. , Smith K.D. , Hume D. , Underhill D.M.
Published: June 2007

Toll-like receptors (TLRs) mediate detection of a broad range of pathogens and pathogen-derived products including LPS, peptidoglycan, bacterial lipopeptides, and lipoteichoic acid. Recent evidence indicates that the broad specificity of TLRs may be a consequence of the interactions between different TLRs. In this report, we demonstrate that while a constitutively active TLR4 homodimer can induce the production of pro-inflammatory cytokines, homodimers of TLR2 and TLR6 cannot. However, when co-expressed in the same cell, constitutively active TLR2 and TLR6 strongly induce cytokine production, indicating that these TLRs require partners to productively signal. Since TLR4 signals as a homodimer, while TLR2 and TLR6 do not, it is clear that, despite the conservation of their cytoplasmic signaling domains, the mechanisms by which they initiate signaling are different. We have localized the region of TLR4 that mediates its ability to signal as a homodimer to the membrane-proximal half of the cytoplasmic tail of the receptor.
MD-2 binds to bacterial lipopolysaccharide
Authors: Viriyakosol S. , Kirkland T.N. , Soldau K. , Tobias P.S.
Published: June 2007

Many LPS binding proteins have been described, but the exact nature of the LPS receptors that signal cells remains unclear. MD-2 is a molecule that is found in association with Toll-like receptor 4, which has been shown to be a receptor for LPS. We have produced human MD-2 in baculovirus and tested it for LPS binding. MD-2 binds the lipid A region of LPS without the need for LPS binding protein. These data suggest that MD-2 may be binding LPS as part of the TLR4 receptor complex.
Plasma constituents regulate LPS binding to, and release from, the monocyte cell surface
Authors: Kitchens Richard L. , Thompson Patricia A. , O'Keefe Grant E. , Munford Robert S.
Published: June 2007

Innate immunity to Gram-negative bacteria involves regulated mechanisms that allow sensitive but limited responses to LPS. Two important pathways that lead to host cell activation and LPS deactivation involve: (i) LPS interactions with CD14 and Toll-like receptor 4 on cells (activation); and (ii) LPS sequestration by plasma lipoproteins (deactivation). Whereas these pathways were previously thought to be independent and essentially irreversible, we found that they are connected by a third pathway: (iii) the movement of LPS from host cells to plasma lipoproteins. Our data show that, in the presence of human plasma, LPS binds transiently to monocyte surfaces and then moves from the cell surface to plasma lipoproteins. Soluble CD14 enhances LPS release from cells in the presence of lipoproteins, whereas LPS binding protein and phospholipid transfer protein do not. The transfer of cell-bound LPS to lipoproteins is accompanied by reduced cell responses to the LPS, suggesting that the movement of LPS from leukocytes into lipoproteins may attenuate host responses to LPS in vivo. Preliminary data suggest that changes that occur in the plasma after trauma or during sepsis decrease LPS binding to leukocytes while greatly increasing the rate of LPS release from cells.
Regulated covalent modifications of lipid A
Authors: Raetz Christian R.H.
Published: June 2007

Regulated covalent modifications of lipid A are implicated in virulence of pathogenic Gram-negative bacteria. The Salmonella PhoP/PhoQ-activated gene pagP is required for resistance to cationic antimicrobial peptides and for biosynthesis of hepta-acylated lipid A species containing palmitate. Interestingly, pagP encodes an unusual enzyme of lipid A biosynthesis localized in the outer membrane, whereas all previously characterized lipid A enzymes are cytoplasmic or associated with the inner membrane. PagP is not unique, however, as pagL encodes another outer membrane enzyme in Salmonella that deacylates the 3 position of lipid A.

S. typhimurium also synthesizes S-2-hydroxymyristate modified lipid A in a PhoP/PhoQ-dependent manner. We postulated that 2-hydroxylation might be catalyzed by a novel dioxygenase. Using well-characterized dioxygenase sequences as probes, tBLASTn searches revealed unassigned open reading frame(s) with similarity to mammalian aspartyl β-hydroxylases in bacteria known to make 2-hydroxyacylated lipid A. The S. typhimurium aspartyl β-hydroxylase homologue ( lpxO) was cloned and expressed in Escherichia coli K-12, which does not contain lpxO. Analysis of the resulting construct revealed that lpxO expression induces O 2-dependent formation of 2-hydroxymyristate-modified lipid A in E. coli. LpxO may be an inner membrane enzyme that catalyzes Fe 2+/ascorbate/α-ketoglutarate dependent hydroxylation of lipid A. We propose that 2-hydroxymyristate released from LPS inside infected animal cells might be converted to 2-hydroxymyristoyl coenzyme A, a potent inhibitor of protein N-myristoyl transferase.
Lipopolyamines as a therapeutic strategy in experimental Gram-negative bacterial sepsis
Authors: Opal Steven M. , Palardy John E. , Parejo Nicolas , Morrison David C.
Published: June 2007

Lipopolyamines are a class of polycationic amphiphilic compounds that have been shown to bind with high affinity to polyanionic macromolecules, including both DNA and bacterial lipopolysaccharide (LPS). One of these compounds, termed DOSPER (1,3-di-oleoyloxy-2-(6-carboxylspermyl)-propylamide), is non-cytotoxic and has been shown to inhibit LPS-mediated cytokine release and lethality in endotoxin challenge models. In the study reported here, the activity of DOSPER was tested in neutropenic rats with invasive Gram-negative bacteremia caused by Pseudomonas aeruginosa. DOSPER alone was ineffective (0/8) at influencing mortality, but provided a significant survival advantage if administered in combination with a bactericidal antibiotic, ceftazidime (10/12; P <0.05). Ceftazidime alone was partially protective (6/12) while the control group had no survivors (0/8). DOSPER administration markedly reduced circulating endotoxin levels ( P <0.01) and interleukin-6 levels ( P <0.05) but had no significant effect on bacteremia and bacterial concentrations of P. aeruginosa in liver or spleen tissue. Lipopolyamines may be potentially valuable as a therapeutic adjunct in treatment of Gram-negative bacterial sepsis.
A novel acute phase marker in cattle: lipopolysaccharide binding protein (LBP)
Authors: Schroedl Wieland , Fuerll Birgitt , Reinhold Petra , Krueger Monika , Schuett Christine
Published: June 2007

The host response to infection, the `acute phase response' is a highly conserved series of physiological reactions including marked changes in concentrations of plasma proteins. These proteins have been shown to participate in the immune response to infections. Several recent studies have elevated the role of acute phase proteins (APPs) as predictive markers in infection. APPs such as serum amyloid A and haptoglobin but not C-reactive protein (CRP) have been identified as markers of inflammation in cattle. In humans, lipopolysaccharide (LPS) binding protein (LBP) has certain biological functions in host defence and participates in acute phase reactions. We measured plasma levels of LBP in a group of 20 calves experimentally infected with Gram-negative Mannheimia haemolytica (Pasteurella) in comparison to haptoglobin, the most widely studied APP in cattle. In infected calves, LBP levels rose significantly 6 h after infection, reaching a maximum at 24 h. Haptoglobin concentrations significantly rose after 12 h, and peak responses were measured 48 h after infection. Thus, LBP may prove to be a diagnostic marker in cattle infection and is faster than haptoglobin in detecting sepsis.
Cytokine synthesis in the liver of endotoxin-tolerant and normal rats during hemorrhagic shock
Authors: Ackermann Marcus , Reuter Martin , Flohé Sascha , Bahrami Soheyl , Redl Heinz , Schade F. Ulrich
Published: June 2007

In the present study the effects of endotoxin tolerance on hemorrhagic shock were investigated with particular focus on hepatic alterations. The following questions were addressed: (i) does hemorrhagic shock induce cytokine formation and heat shock response in the liver; and (ii) does endotoxin tolerance alter these reactions. Endotoxin tolerance was induced by repetitive daily injections of LPS for 5 days. Hemorrhagic shock was induced by hypovolemia (MAP 35 ± 5 mmHg). After 3 h, the animals were resuscitated by re-infusion of homologous blood. m-RNA was isolated from liver biopsies and the mRNA levels of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), interleukin-10 (IL-10) and heat shock protein 70 (HSP-70) were determined by RT-PCR. TNF-α was measured by ELISA in serum samples and in the supernatants of whole blood cultures. It was found that endotoxin tolerance reduced mortality caused by hemorrhagic shock from 80% to 20%. In parallel, TNF-α production in response to LPS in vivo and in vitro was significantly decreased. During hemorrhage and after resuscitation. increased mRNA levels were detected in hepatic biopsies for TNF-α, IL-6, IL-10 and HSP-70, with highest levels immediately after re-infusion. Endotoxin-tolerant rats produced significantly lower levels of TNF-α, while no differences were found for IL-10 and HSP-70. Within 30 min after reperfusion, significantly higher levels of IL-6 mRNA were found in hepatic biopsies from tolerant rats; these differences disappeared 2 h after reperfusion.
Structural and serological characterisation of the O-antigenic polysaccharide of the lipopolysaccharide from Acinetobacter strain 96 (DNA group 11)
Authors: Vinogradov Evgeny V. , Pantophlet Ralph , Brade Helmut , Holst Otto
Published: June 2007

A polysaccharide containing D-Man p, L-Fuc p (6-deoxygalactopyranose, fucose) and D-Glc pNAc was isolated by mild acid hydrolysis, followed by gel-permeation chromatography, from the lipopolysaccharide derived from Acinetobacter strain 96 (DNA group 11). The structure of the O-antigen was determined by compositional analysis and NMR spectroscopy of the polysaccharide as:

A monoclonal antibody obtained after immunization of mice with heat-killed bacteria of Acinetobacter strain 96 was shown to bind to the O-antigen and did not cross-react with any Acinetobacter O-antigen of known structure.
TNF-α hyper-responses to Gram-negative and Gram-positive bacteria in Propionibacterium acnes primed or Salmonella typhimurium infected mice
Authors: Merlin Thomas , Gumenscheimer Marina , Galanos Chris , Freudenberg Marina A.
Published: June 2007

IFN-γ-dependent hypersensitivity to LPS is inducible in mice by infection or pre-treatment with killed bacteria. Hypersensitive mice exhibit enhanced inflammatory responses to LPS, including the overproduction of TNF-α. Using Lpsn BALB/c and Lpsd BALB/c/l mice, primed with Propionibacterium acnes or infected with Salmonella typhimurium, we show that concurrently to hypersensitivity to LPS, a hypersensitivity to other constituents of killed Gram-negative or Gram-positive bacteria and to staphylococcal enterotoxin B (SEB) develops. The TNF-α hyper-responses in sensitized mice induced by different Gram-positive bacteria, are generally weaker than those by Gram-negative bacteria and vary significantly, due to the absence of a common, LPS-equivalent component. Using IFN-γR—/— and the respective wild-type mice, we demonstrate that although sensitization to LPS and killed Listeria monocytogenes is exclusively IFN-γ-dependent, an IFN-γ-independent, moderate sensitization to certain TNF-α-inducing constituents in bacteria may develop in parallel.
Invited review: Bacterial lipopolysaccharides and innate immunity
Authors: Alexander Christian , Rietschel Ernst Th.
Published: June 2007

Bacterial lipopolysaccharides (LPS) are the major outer surface membrane components present in almost all Gram-negative bacteria and act as extremely strong stimulators of innate or natural immunity in diverse eukaryotic species ranging from insects to humans. LPS consist of a poly- or oligosaccharide region that is anchored in the outer bacterial membrane by a specific carbohydrate lipid moiety termed lipid A. The lipid A component is the primary immunostimulatory centre of LPS. With respect to immunoactivation in mammalian systems, the classical group of strongly agonistic (highly endotoxic) forms of LPS has been shown to be comprised of a rather similar set of lipid A types. In addition, several natural or derivatised lipid A structures have been identified that display comparatively low or even no immunostimulation for a given mammalian species. Some members of the latter more heterogeneous group are capable of antagonizing the effects of strongly stimulatory LPS/lipid A forms. Agonistic forms of LPS or lipid A trigger numerous physiological immunostimulatory effects in mammalian organisms, but — in higher doses — can also lead to pathological reactions such as the induction of septic shock. Cells of the myeloid lineage have been shown to be the primary cellular sensors for LPS in the mammalian immune system. During the past decade, enormous progress has been obtained in the elucidation of the central LPS/lipid A recognition and signaling system in mammalian phagocytes. According to the current model, the specific cellular recognition of agonistic LPS/lipid A is initialized by the combined extracellular actions of LPS binding protein (LBP), the membrane-bound or soluble forms of CD14 and the newly identified Toll-like receptor 4 (TLR4)*MD-2 complex, leading to the rapid activation of an intracellular signaling network that is highly homologous to the signaling systems of IL-1 and IL-18. The elucidation of structure-activity correlations in LPS and lipid A has not only contributed to a molecular understanding of both immunostimulatory and toxic septic processes, but has also re-animated the development of new pharmacological and immunostimulatory strategies for the prevention and therapy of infectious and malignant diseases.
Porins from Salmonella typhimurium accelerate human blood coagulation in vitro by selective stimulation of thrombin activity: implications in septic shock DIC pathogenesis
Authors: Di Micco B. , Metafora S. , Colonna G. , Cartenì M. , Ragone R. , Macalello M.A. , Di Micco P. , Baroni A. , Catalanotti P. , Tufano M.A.
Published: June 2007

The effect of porins, major hydrophobic outer membrane proteins purified from Salmonella typhimurium , on human blood coagulation was investigated. It was found that micromolar concentrations of porins accelerated markedly human blood coagulation in vitro. Using appropriate experiments, data were obtained showing that the main target of the porin-induced procoagulant effect was thrombin. A possible binding of porins with thrombin has been suggested to be the basis of this effect. The implications of this finding in the pathogenesis of the disseminated intravascular coagulation syndrome (DIC) occurring during the Gram-negative septic shock is discussed.
The crucial role of systemic responses in the innate (non-adaptive) host defense
Authors: Munford Robert S. , Pugin Jérome
Published: June 2007

We suggest that successful defense against microbial invasion requires both local inflammation and systemic anti-inflammation. The key systemic responses involve the hypothalamic-pituitary-adrenocortical axis, the sympathetic-adrenomedullary axis, acute phase protein production, thermoregulation and alterations in leukocyte responsiveness to agonists such as bacterial endotoxin. These integrated responses raise blood and tissue concentrations of several anti-infective molecules, mobilize leukocytes into the circulation, and increase blood flow to injured or infected sites. They also neutralize cytokines, proteases and oxidants that enter the bloodstream from inflamed local sites and forestall endothelial activation in distant vessels. Together, these forces help concentrate activated phagocytes at injured or infected local sites while preventing potentially damaging inflammation in uninvolved tissues.
Toll-like receptor-2 transduces signals for NF-κB activation, apoptosis and reactive oxygen species production
Authors: Aliprantis Antonios O. , Weiss David S. , Zychlinsky Arturo
Published: June 2007

The innate immune system coordinates the inflammatory response to pathogens. To do so, cells of the innate immune system must rapidly discriminate between self and non-self. All bacteria express membrane-associated lipoproteins. These molecules activate cells of the innate immune system to initiate host defense mechanisms. However, it is currently unknown how the innate immune system recognizes bacterial lipoproteins. Here, we describe that in response to bacterial lipoprotein, human Toll-like receptor-2 activates three different cellular responses: nuclear factor-κB dependent transcription, programmed cell death and reactive oxygen species production. We propose that Toll-like receptor-2 fulfils multiple roles in the genesis of the immune response to bacterial pathogens.
Scavenger receptor-like receptors for the binding of lipopolysaccharide and lipoteichoic acid to liver endothelial and Kupffer cells
Authors: van Oosten Marijke , van Amersfoort Edwin S. , van Berkel Theo J.C. , Kuiper Johan
Published: June 2007

This study was undertaken to identify the role of scavenger receptors in the catabolism of lipopolysaccharide (LPS) and lipoteichoic acid (LTA). LPS is mainly cleared from the blood by the liver. The Kupffer cells are primarily responsible for this clearance. Although several binding sites have been described for LPS and LTA, only CD14 is involved in LPS signalling. Scavenger receptor type A (SR-A) is expressed in the liver on endothelial cells and Kupffer cells, and macrosialin (class D scavenger receptor) is expressed on Kupffer cells. Fucoidin and poly-I are both good inhibitors of scavenger receptors. Fucoidin significantly reduced the serum clearance of [125I]-LPS and decreased liver uptake of [125I]-LPS by ~40%. Poly-I inhibited the binding of [125I]-LPS to isolated Kupffer and endothelial cells by 75%, while poly-A, a polyanionic substrate that does not block scavenger receptors, had no effect. LPS significantly inhibited the binding of acetylated LDL and oxidized LDL (two well-described scavenger receptor ligands) to isolated Kupffer and liver endothelial cells. OxLDL and acLDL did not affect the binding of LPS to these cells. We conclude that on both endothelial cells and Kupffer cells, LPS mainly binds to scavenger receptors, but SR-A and macrosialin contribute to a limited extent to the binding of LPS. Injection of LTA into C57Bl6 mice resulted in a maximal liver uptake of 20% of the injected dose. In the liver, 50% was bound by the Kupffer cells, 20% by parenchymal cells and 30% by liver endothelial cells. The contribution of SR-A to the plasma clearance of LTA was limited. A main component in the catabolism of LTA is the interaction of LTA with plasma lipoproteins, which limit the uptake of LTA by tissues and extend the plasma half-life of LTA.
Pathophysiological relevance of the CD14 receptor in surgical patients: biological activity of endotoxin is regulated by the CD14 receptor
Authors: Hiki Naoki , Mimura Yoshikazu , Ogawa Toshihisa , Kojima Junichi , Hatao Fumihiko , Kaminishi Michio
Published: June 2007

Endotoxins (lipopolysaccharides, LPSs) are potent bacterial poisons, and they are always present in the intestine in considerable numbers. Stress, such that as a resulting from multiple injuries, burns, hypovolemia, hypoxia, intestinal ischemia, and surgery can lead to a breakdown of the gut barrier, allowing endotoxins to enter the systemic circulation via translocation. However, estimating the biological activity of translocated circulating endotoxins and identification of the mechanisms regulating their biological activities remain complex problems. CD14 has been found to exist as a soluble protein in the serum and as a glycosylphosphatidylinositol (GPI)-anchored protein of myeloid lineage cells. It plays key roles in both LPS-induced activation and in LPS internalization by cells. In this article, we outline: (i) the biological activity of circulating endotoxin; and (ii) the role of membrane and/or soluble CD14 regulating the bioactivity of circulating endotoxin in a human model of postoperative endotoxemia.