bluuebunny/crossref_metadata_2025 huggingface dataset:
I Set a Table before You: The Jewish Eschatological Character of Aseneth’s Conversion Meal
Authors: Lieber Andrea
Published: June 2007

Food is a powerful symbol in Joseph and Aseneth in that it sharply defines the social boundaries that are so important to the text as a whole. Jews and Gentiles portrayed in the novella differ primarily with respect to their theological beliefs, and this difference is both reflected and incorporated through acts of eating. Employing classical anthropological and sociological approaches to the relationship between sacrificial meals and kinship, this essay explores the symbolic and literary function of the conversion meal in Joseph and Aseneth. Viewed as a symbolic expression of mediation between humanity and the divine, Aseneth’s meal is compared with similar passages from Philo and Rabbinic literature that depict mystical or eschato-logical meal scenes.
Ronald Preston, William Temple, and the Future of Christian Politics
Authors: Chapman Mark D.
Published: June 2007

This article discusses Ronald Preston's understanding of William Temple and the relationships between the two thinkers. It shows how both develop a theology of Christian realism which places great emphasis on the autonomy of the social sciences and the importance of economic expertise. Questions are raised about the appropriateness of this method, as well as their understanding of the state as an order of creation: these can easily lead to the reduction of the sphere of political morality and its substitution with a form of technical rationality. After a brief discussion of the cult of the expert and the manager in contemporary British politics, and the limitation of political action through the rhetoric of ‘there is no alternative', the article concludes by calling for a remoralisation of political life against an economic reductionism which threatens to remove ethics from politics altogether.
Baan Mankong: going to scale with “slum” and squatter upgrading in Thailand
Authors: Boonyabancha Somsook
Published: June 2007

This paper describes the ambitious national slum and squatter upgrading programme launched by the Thai government in 2003 and implemented through the Community Organizations Development Institute (CODI). The programme centres on providing infrastructure subsidies and housing loans to low-income communities to support upgrading in situ wherever possible and, if not, to develop new homes close by. Support is provided not only to community organizations formed by the urban poor for projects but also to their networks, to allow them to work with city authorities and other local actors and with national agencies on city-wide upgrading programmes. It seeks to “go to scale “ by supporting thousands of community-driven initiatives within citywide programmes designed and managed by urban poor networks working in partnership with local actors. The paper gives some background information about CODI and its predecessor the Urban Community Development Office, before describing the national upgrading programme.
`What do Girls Know Anyway?': Rationality, Gender and Social Control
Authors: Oliver Pam
Published: June 2007

Within psychology, as in other areas of science, rationality continues to be equated largely with the rules of logic and objectivity. It is also associated typically with masculinity. Psychological theories of rationality and of gender have been used, consciously or otherwise, as an effective social control strategy in the continuing social suppression of women, by portraying them as more suited to subordinate social roles. This paper shows how this has occurred through the imposition and maintenance of rules and ideologies based on rationality as objective logic. In order for the current locus of male social control to shift, several changes are necessary, including the recognition that rationality involves more than logic and that women's knowledge and its expression have their own equal validity.
The Mother as Container: Placental Process and Inner Space
Authors: Raphael-Leff Joan
Published: June 2007

An unconscious paradigm informing psychosocial structuring of mothers is explored: the initial placental interchange of nutrients and waste between pregnant woman and foetus, serves as metaphor/model for postnatal interaction, when a mother contains and metabolizes her preverbal infant `s unbearable anxieties, returning them in tolerable form. Unconscious conflation of placental process with maternal functioning perpetuates female primary care, privileging biological mothers. On a societal level, unconscious residues of universal early transactions with female primary caregivers, promote women as nurturing/waste-disposing `placental containers'. This projection has wider cultural manifestations in the simultaneous idealization of mothers and devaluation of both women and maternal function. Creative inner space, attainable by internalizing the primary caregiver-as-container is confounded with female procreative space resulting in women being exploited as repositories for containment of male cultural productivity and waste.
Asian Women's Ethnic Identity: The Impact of Gender and Context in the Accounts of Women Bringing Up Children in East London
Authors: Woollett Anne , Marshall Harriette , Nicolson Paula , Dosanjh Neelam
Published: June 2007

This study examines the ways in which a group of women of Asian origin or descent define and discuss aspects of ethnicity and ethnic identity. Thirty-two Asian women of different religious and cultural backgrounds who were bringing up young children in East London were interviewed by an Asian psychologist. As part of a more extensive interview about childbirth, child care and child rearing, women were asked about their ethnic identity. Their accounts indicate that their constructions of ethnicity and ethnic identity are fluid and changing, taking account of gender, developmental changes associated with motherhood and the context of their lives as mothers of young children. Analysis of their accounts is used to argue that ethnicity and ethnic identity are not homogeneous categories, that they operate across gender and, therefore, greater consideration needs to be given in developmental psychology to the complexity and variations in women's representations of ethnicity.
Safety, Danger and the Movies: Women's and Men's Narratives of Aggression
Authors: Squire Corinne
Published: June 2007

Most stories about aggression belong either to the `Insider Gothic' or to the `Outsider Gothic' narrative genre, both of which are common in contemporary films. Through these genres, both women and men express and develop ambivalent relationships with aggression: these include fear and resistance, pleasure and condemnation. Within the narratives, though, zones of safety are much narrower for women than for men, and resistance is more private.
The Good-Enough Father of Whatever Sex
Authors: Samuels Andrew
Published: June 2007

Political focus on the family, especially lone-parent families, puts psychoanalytic developmental psychology at the centre of public debate. This article argues that there are no inevitable negative psychological consequences of lone parenthood or parenting carried out by two or more persons of the same sex. It introduces two new concepts/images to clarify the issues: `the good-enough father' and `the father of whatever sex'. These concepts/images enable us to address two linked issues: the `lone mother question' and the `crisis in fatherhood question'. The author's previous work on fathering and on the psychology of contemporary Western politics is employed as the basis for a political challenge to most psychoanalytic accounts of the father-child relationship as well as to conventional political wisdom about the family.
Daring to Presume
Authors: Livia Anna
Published: June 2007

This article asks whether it is presumptuous for afeminist writer to create characters quite different from herself. Using the particular example of heterosexual novelists' representations of lesbians, it argues that such presumption-although fraught with difficulties-is essential to feminist truth-telling.
Thinking through Class: The Place of Social Class in the Lives of Young Londoners
Authors: Phoenix Ann , Tizard Barbara
Published: June 2007

Current debates about the utility of the concept of social class for social analysis have been helpful in illuminating the shortcomings of traditional theories and traditional methods of assessment of social class. Yet, social class continues to have an important impact on life chances and worldviews. This article uses data from an interview study of 248 young Londoners (young women and men; black, white and of `mixed-parentage') to examine the place of social class in young people's lives. The young people's accounts indicated that they did not necessarily use occupational groupings in defining social class and that the majority considered themselves to be middle class. Nonetheless, social class was important to the ways in which they thought about themselves. They differentiated themselves from others on the basis of differences in lifestyle, housing, money, speech, dress and behaviour. Some disliked and/or feared people they considered to be from other social classes.
The Social Identities of Female Leaders in Different Cultural Contexts
Authors: Rojahn Krystyna , H. Fischer Agneta , Willemsen Tineke M.
Published: June 2007

This paper examines the meanings of womanhood as part of female leaders' social identities in relation to the different socio-cultural contexts of Poland and the Netherlands. The empirical study consists of interviews about gender and leadership with 25 female leaders in each country. A combination of content analysis and discourse analysis techniques was used in order to interpret the interviews. The results show both similarities and differences between the two samples in approaching the relevance of womanhood in the context of leadership. The interviewees' reactions are discussed from the perspective of the different inter-gender relationships in each country.
Men and the Discursive Reproduction of Sexism: Repertoires of Difference and Equality
Authors: Gough Brendan
Published: June 2007

Discourses around masculinities have recently attracted critical attention from feminist social psychology. The present paper contributes to this field by problematizing talk around gender equality in the context of all-male group discussions. Two broad patterns of accounting which promulgated male superiority were identified - appeals to gender difference/dominance and egalitarian ideals. The invocation of gender difference was grounded variously in `socialization', `biology' and the `psychology of women' repertoires. It is argued that such accounts of stable gender differences are ideological, in that they mask oppression by rendering existing power relations natural and inevitable. As well, and somewhat paradoxically, the articulation of liberal values assisted in the formulation of sexist sentiment. This particular discursive strategy has been well documented with respect to `new racism' and only recently studied in the context of sexism. The discursive reproduction of inequalities is clearly an important feminist issue and the ideological import of such talk is discussed.
Who's the Boss? Confronting Whiteness and Power Differences within a Feminist Mentoring Relationship in Participatory Action Research
Authors: McIntyre Alice , Lykes M. Brinton
Published: June 2007

In this article, we discuss the sometimes problematic and always challenging nature of feminist mentoring, particularly in a participatory action research project aimed at interrogating whiteness. We analyze our relationship by examining the multiple contexts in which it was embedded-power relations within the institution in which the research was conducted, our expectations of one another both during and after the research experience, our complementary and conflicting agendas, whiteness, social class and gender. We illuminate the nuanced complexities of our relationship providing feminist researchers and scholars with a lens that elucidates the kaleidoscope that is woman-to-woman academic relationships. Our experiences suggest possible strategies for white educators and researchers who seek to both rethink the meaning of whiteness and reimagine feminist mentoring relationships through creating liberatory research methodologies. In addition, we suggest that as feminist researchers we need to continually demonstrate our reflexivity through (re)articulating how we problematize power, privilege and the multiple unequal hierarchies that exist in feminist research.
Strategies of Resistance: `Bad' Mothers Dispute the Evidence
Authors: Croghan Rosaleen , Miell Dorothy
Published: June 2007

Previous research has focused on the ways in which women who are clients of welfare agencies are constructed by professional discourse. In contrast, the present study looks at the ways in which women who are designated as `problem mothers' take issue with these professional definitions. A discourse-analytic approach is adopted in the analysis of the strategies of accommodation and resistance employed by such women. Particular attention is paid to the ways in which women seen as `bad mothers' position themselves within existing frameworks of `good mothering' and professional practice in order to establish the right to be heard. The analysis highlights some of the strategies through which such women can attempt to construct a positive maternal identity whilst negotiating for effective help from welfare agencies. Some of the implications of the enmeshment of resistance in appeals to common values are discussed, together with implications for professional practice.
The Pentecostal Significance of Numbers 11
Authors: Cotton Roger
Published: June 2007

Numbers 11 describes a very significant interconnectedness of the Spirit of God and leadership/ministry of God's people and prophetic activity. This is established as the LORD answered the first great need of Moses in leading the people of Israel on the journey through the wilderness of the Promised Land with a special demonstration of his Spirit. The empowering of the 70 elders accompanied by a prophetic experience foreshadowed the Acts 2— Pentecost event. Therefore, Number 11 should be considered as the foundational Charismatic/Pentecostal passage in the Old Testament.
What Meaneth This? Pentecostals and Theological Inquiry
Authors: Coulter Dale
Published: June 2007

This article investigates what it means to maintain a Pentecostal theology by asking whether Pentecostals have any theological distinctives to offer, and, if so, how they may be identified. The first part begins with two recent approaches that seek to articulate what is theologically distinctive for Pentecostals through an appeal to spiritual experience. Following a critique of those approaches, the author proposes a constructive framework within which theological distinctives may emerge. The article concludes by applying the framework to the doctrine of scripture as a test case in order to determine what may be theologically distinct in the Pentecostal confession about that doctrine.
Toward a Theology of Pentecostal Preaching
Authors: Gordy John
Published: June 2007

In spite of the recent surge of scholarship within the Pentecostal community during the past two decades, only a scarce amount of research and critical reflection has been devoted to the area of Pentecostal preaching. This article seeks to address that void by exploring the uniqueness of Pentecostal preaching, its internal dynamics and parameters, and proposing a framework to construct a theology of Pentecostal preaching.
The Church and the Development of Doctrine
Authors: Chan Simon
Published: June 2007

Doctrines are the authoritative teachings of the Church, yet the modern church is hampered by its inability to speak authoritatively even to its own members on matters of doctrine. One reason is that doctrines are widely perceived as archaic and fixed formulations with little significance for the present day. True doctrines, in fact, are constantly developing as the Church moves towards eschatological fulfillment. Yet for doctrines to develop properly there needs to be a proper ecclesiology. The Church is not an entity that God brought into being to return creation to its original purpose after the Fall; rather, the Church is prior to creation, chosen in Christ before the creation of the world (Eph. 1.4). It is a divine-humanity, ontologically linked to Christ the Head. It is the living Body of Christ, the totus Christus.Within the continuing life of prayer and worship, the Church’s doctrines are re-enacted, renewed and developed. These acts constitute the ecclesial experience or the living tradition. The living tradition is the transmission and development of the gospel of Jesus Christ in the on-going practices of the Church through the power of the Holy Spirit. The coming of the Spirit upon the Church at Pentecost is not just to enable the Church to preach the gospel but to constitute the Church as part of the gospel itself. That is to say, the gospel story includes the story of the Spirit in the Church. The third person of the Godhead is revealed as such in his special relation to the Church. The Church, therefore, could be called the ‘polity of the Spirit’, that is, the public square in which the Spirit is especially at work to bring God’s ultimate purpose to fulfillment. There is, therefore, no separation between ecclesiology and pneumatology. They are necessary for maintaining the living tradition and ensuring the healthy development of doctrine until the Church attains unity of the faith. Pentecostals who see the Pentecost event as the distinctive mark of their identity have a special role to play: by becoming more truly catholic in their ecclesiology, they become more truly Pentecostal. This accords well with their early ecumenical instinct.
Nourishment for our Journey: The Pentecostal Via Salutis and Sacramental Ordinances
Authors: Archer Kenneth
Published: June 2007

Sacramental ordinances are community acts of commitment ordained by Christ as means of grace with particular symbolic significance for our Pentecostal identity (story) and faith journey (via salutis). By locating the sacramental ordinances in the Pentecostal story, the sacramental ordinances take on a spiritual-metaphorical-narrative nature. The metaphorical and narrative nature of the sacraments gives the Holy Spirit opportunity to work redemptively in our lives by strengthening the community in her journey (via salutis) thus (re) shaping Pentecostal identity as the eschatological people of God.
Reversible binding of heparin to the loop peptide of endotoxin neutralizing protein
Authors: Ridge Richard J. , Paus Erik J. , Novitsky Thomas J. , Ketchum Paul A.
Published: June 2007

Endotoxin neutralizing protein (ENP) from Limulus polyphemus is an amphipathic, 11.8 kDa protein with an isoelectric point of 10.2. ENP neutralizes lipopolysaccharide (LPS) and possesses antibacterial activity against Gram-negative bacteria. Heparin binds to ENP and blocks its LPSneutralizing activity. The relative blocking activity of heparin is equal to low molecular weight heparin and polyanetholsulfonic acid > heparan sulfate > chondroitin sulfate A > chondroitin sulfate C. Endoproteinase Glu-C hydrolysis of recombinant ENP results in four major peptides, three of which are seen following separation on reversed phase HPLC. Heparin binds to the loop peptide (31—72), which includes the heparin binding consensus sequence XBBXBX between the two cysteine residues of ENP. When heparin is added to the digest and then applied to a C18 column, the loop peptide is bound; however, it dissociates and elutes with either 5 M NaCl or 0.1 M sodium phosphate, demonstrating reversible binding to heparin. LPS and lipid A both bind to the loop peptide and remove it from digests of ENP; however, neither complex could be dissociated by salt or sodium phosphate. Heparin, LPS, and lipid A individually bind to the same site on ENP.
Review: The search for Lps: 1993—1998
Authors: Beutler Bruce , Poltorak Alexander
Published: June 2007

For the sake of coherence, this account is written chiefly in the person of the first author, though it represents the joint recollection of both authors, who were party to the cloning of Lps. Numerous dates and events were reconstructed based upon meticulous records kept by Betsy Layton, Administrative Assistant to the first author, who also participated in the cloning effort. Scientific citations are indicated in superscript and are to be found under References; comments are indicated as { n} and are to be found under Notes (section before References).
Phase variation of Coxiella burneti0i strain Priscilla: influence of this phenomenon on biochemical features of its lipopolysaccharide
Authors: Ftácek Peter , Skultéty L'udovít , Toman Rudolf
Published: June 2007

During the phase variation of Coxiella burnetii, modifications in its lipopolysaccharide (LPS) component were investigated. The cloned phase I C. burnetii cells were passed serially in chicken embryo yolk sacs up to the egg passage (EP) 90. The LPSs from the cells in EPs 3, 12, 21, 40, 60, and 90 were all separated by steric exclusion chromatography into three major populations: the high, intermediate, and low molecular weight fractions, differing one from another in size and chemical composition. No noticeable shortening of the O-polysaccharide chains was observed in the LPSs isolated during the C. burnetii cultivation. However, a redistribution of the existing LPS populations has been observed due to an increasing prevalence of those cells in the whole cell population that express LPS molecules with truncated O-chains and those being of R-type. In the high and intermediate molecular weight LPS populations, virenose and dihydrohydroxystreptose are lost gradually with the progress in phase variation. This occurs more readily with the former sugar. At present, the molecular mechanisms influencing the LPS modifications during the C. burnetii phase variation remain unclear.
Review: The lipemia of sepsis: triglyceride-rich lipoproteins as agents of innate immunity
Authors: Harris Hobart W. , Gosnell Jessica E. , Kumwenda Zindaba L.
Published: June 2007

Bacterial endotoxin (LPS) elicits dramatic responses in the host including elevated plasma lipid levels due to the increased synthesis and secretion of triglyceride (TG)-rich lipoproteins by the liver, and the inhibition of lipoprotein lipase. This cytokine-induced hyperlipoproteinemia, clinically termed the `lipemia of sepsis', was customarily thought to represent the mobilization of lipid stores to fuel the host response to infection. However, since lipoproteins can also bind and neutralize LPS, we hypothesize that TG-rich lipoproteins (VLDL and chylomicrons) are also components of an innate, non-adaptive host immune response to infection. Herein we review data demonstrating the capacity of lipoproteins to bind LPS, protect against LPS-induced toxicity, and modulate the overall host response to this bacterial toxin. Lastly, we propose a pathway whereby lipoprotein-bound LPS may represent a novel, endogenous mechanism for regulating the hepatic acute phase response.
Molecular mechanisms of NF-κB activation induced by bacterial lipopolysaccharide through Toll-like receptors
Authors: Guolong Zhang  , Ghosh Sankar
Published: June 2007

Septic shock, caused by exaggerated host responses to various microbial products typified by lipopolysaccharide (LPS), remains the leading cause of death in trauma patients. Gaining insight into the nature of host interactions with LPS will certainly facilitate attempts to develop effective anti-sepsis drugs. Tremendous progress has been made during the past few years in understanding the mechanisms of pathogen-induced host responses. Toll-like receptor (TLR) 4 and 2 have been implicated as major receptors for signaling initiated by LPS and many other microbial products following their binding to CD14. In addition, many signaling intermediates involved in LPSinduced cell activation, particularly activation of the transcription factor NF-κB, have been identified and characterized. Further investigations with these molecules will certainly reward us with more effective therapeutic drugs to treat septic shock as well as many other inflammatory and infectious disorders.
Structural variability and originality of the Bordetella endotoxins
Authors: Caroff Martine , Aussel Laurent , Zarrouk Hassan , Martin Adèle , Richards James C. , Thérisod Hélène , Perry Malcolm B. , Karibian Doris
Published: June 2007

Structural studies of Bordetella endotoxins (LPSs) have revealed remarkable differences: (i) between their LPSs and those of other bacterial pathogens; (ii) among the LPSs of the seven identified Bordetella species; and (iii) among the LPSs of some Bordetella strains. The lipid As have the `classical' bisphosphorylated diglucosamine backbone but tend to have fewer and species-specific fatty acid components compared to those of other genera. Nevertheless, three strains of B. bronchiseptica have at least three different fatty acid distributions; however, the recently identified B. hinzii and B. trematum LPSs had identical lipid A structures. The B. pertussis core is a dodecasaccharide multi-branched structure bearing amino and carboxylic groups. Another unusual feature is the presence of free amino sugars in the central core region and a complex distal trisaccharide unit containing five amino groups of which four are acetylated and one is methylated. The B. pertussis LPS does not have O-chains and that of B. trematum had only a single O-unit, unlike the LPSs of all the other species of the smooth-type. The O-chain-free cores of non- B. pertussis LPSs were always built on the B. pertussis core model but most were species-specifically incomplete. The LPS structures of three B. bronchiseptica strains were found to be different from each other. The O-chains of B. bronchiseptica and B. parapertussis were almost identical and had some features in common with B. hinzii O-chain. Serological analyses are consistent with the determined LPS structures.
Structural and biological characterisation of a novel tetra-acyl lipid A from Escherichia coli F515 lipopolysaccharide acting as endotoxin antagonist in human monocytes
Authors: Zähringer Ulrich , Salvetzki Ralf , Wagner Frauke , Lindner Buko , Ulmer Artur J.
Published: June 2007

We here report on the structural analysis of a novel tetra-acyl lipid A (LAtetra) isolated from Escherichia coli deep rough (Re)-mutant strain F515. In addition to the biologically active hexa-acyl E. coli-type lipid A (compound 506), this incompletely acylated lipid A was found to be also present in the native LPS. Its structure was studied without further derivatisation by chemical analysis, matrix-assisted laser desorption/ionization mass spectrometry, and one- and two-dimensional 1H- and 13C-NMR spectroscopy. It was found to be structurally distinct from the tetraacyl lipid A biosynthetic precursor Ia (compound 406) in lacking the primary ( R)-3-hydroxytetradecanoic acid 14:0(3-OH) in position 3′ ester-linked to the `non-reducing' glucosamine (GlcN II). The hydroxyl group at the ( R)-3-hydroxytetradecanoic acid attached to position 2′ of GlcN II was found to be substituted by dodecanoic acid (12:0), thus forming a dodecanoyloxytetradecanoyl residue 14:0[3- O(12:0)]. The acylation pattern at the `reducing' GlcN I was identical to that of compound 406 in having two primary ( R)-3-hydroxy tetradecanoic acid residues [14:0(3-OH)] attached to positions 3 (ester-linked) and 2 (amide-linked), respectively. In human mononuclear cells (hMNC) the new LAtetra antagonized LPS-induced release of interleukine-1 (IL-1), interleukine-6 (IL-6), and tumor necrosis factor (TNF) in a dose-dependant manner with identical antagonistic potency as compared with compound 406. Also like compound 406, it was found to be an agonist in murine macrophage-like J774.1 cells.
Signal integration in lipopolysaccharide (LPS)-stimulated murine macrophages
Authors: Vogel Stefanie , Hirschfeld Matthew J. , Perera Pin-Yu
Published: June 2007

Using a panel of LPS-inducible genes, selected for the capacity of their products to contribute to endotoxicity, normal macrophages were compared to macrophages deficient in CD14, CD11b/CD18, or TLR4 to elicit gene expression in response to Escherichia coli LPS or the LPS mimetic, Taxol. All genes were TLR4-dependent. At low doses of LPS or Taxol, all genes were also CD14-dependent; however, IP-10 and ICSBP remained poorly inducible even at much higher concentrations. A distinct subset of genes (COX-2, IL-12 p40, and IL-12 p35) was CD11b/CD18-dependent. NF-κB translocation and MAPK phosphorylation were dysregulated in receptor-deficient macrophages. In contrast to E. coli LPS, a Porphyromonas gingivalis LPS preparation was found to be TLR2-, rather than TLR4-dependent, and resulted in differential expression of genes within the panel. These data suggest that: (i) TLR4 is necessary, but not sufficient, to induce the full repertoire of genes examined; (ii) CD14 and CD11b/CD18 facilitate signaling for induction of select subsets of genes that are also TLR4-dependent; and (iii) signaling through TLR2 versus TLR4 differs quantitatively/qualitatively. These data support an LPS signaling complex on murine macrophages that minimally includes CD14, CD11b/CD18, and TLR4 to respond to E. coli LPS to elicit the full spectrum of gene expression.
Moesin: a potential LPS receptor on human monocytes
Authors: Amar Salomon , Oyaisu Kosuke , Li Li  , Van Dyke Thomas
Published: June 2007

Bacterial endotoxin (lipopolysaccharide, LPS), a glycolipid found in the outer membrane of Gram-negative bacteria, induces the secretion of pro-inflammatory cytokines such as tumor necrosis factor alpha (TNF-α), interleukin (IL)-1, and IL-6 by monocytes/macrophages. The secretion of these biologically active compounds leads to multiple pathological conditions, such as septic shock. There is substantial evidence that chronic exposure to LPS in periodontal diseases mediates, at least in part, the tissue destruction associated with the Gram-negative infection. LPS receptor has been shown to be CD14, a 55 kDa protein. LPS—CD14 interactions mediate many monocyte/macrophage functions in the inflammatory response. However, CD14 lacks a cytoplasmic domain, or any known signal transduction sequence motif, suggesting the existence of another cell surface domain capable of transducing signals. More recently, significant work has implicated Toll proteins in LPS-mediated signaling. The purpose of the present work was to investigate, identify, and characterize secondary LPS binding cell surface domain(s) on monocytes/macrophages. Initial experiments with anti-CD14 blocking antibody revealed only partial blocking of the LPS induced TNF-α response. The kinetics of these experiments suggested a second, low-affinity receptor. Cross-linking experiments were performed to identify LPS binding sites. Two domains were identified: a 55 kDa protein which was inhibited by anti-CD14 (presumably the CD14 receptor) and a second 78 kDa domain. Partial protein sequencing of the 78 kDa domain using mass spectroscopic analysis ascribed this domain to Moesin (membrane organizing extension spike protein). Preliminary experiments using anti-Moesin monoclonal antibody revealed a dose-dependent blocking of LPS induced TNF-α response with a total blocking at 50 µg/ml. Irrelevant isotype controls had no effect. Additional experiments were performed to evaluate the specificity of the anti-Moesin blocking. Separate experiments evaluated anti-Moesin effects on monocyte chemotaxis, IL-1 production in response to IL-1 stimulation, and TNF-α secretion in response to Staphylococcus aureus stimulation. Anti-Moesin antibody only blocked LPS-mediated events. Histological analysis of tissue sections harvested from LPS-induced skin lesions exhibited a 3-fold reduction of the polymorphonuclear neutrophil infiltrate in Moesin-deficient mice compared to wild type mice. The data suggest that Moesin functions as an independent LPS receptor on human monocytes.
Invited review: Neisseria meningitidis lipopolysaccharides in human pathology
Authors: Brandtzaeg Petter , Bjerre Anna , Øvstebø Reidun , Brusletto Berit , Joø Gun Britt , Kierulf Peter
Published: June 2007

Neisseria meningitidis causes meningitis, fulminant septicemia or mild meningococcemia attacking mainly children and young adults. Lipopolysaccharides (LPS) consist of a symmetrical hexa-acyl lipid A and a short oligosaccharide chain and are classified in 11 immunotypes. Lipid A is the primary toxic component of N. meningitidis . LPS levels in plasma and cerebrospinal fluid as determined by Limulus amebocyte lysate (LAL) assay are quantitatively closely associated with inflammatory mediators, clinical symptoms, and outcome. Patients with persistent septic shock, multiple organ failure, and severe coagulopathy reveal extraordinarily high levels of LPS in plasma. The cytokine production is compartmentalized to either the circulation or to the subarachnoid space. Mortality related to shock increases from 0% to > 80% with a 10-fold increase of plasma LPS from 10 to 100 endotoxin units/ml. Hemorrhagic skin lesions and thrombosis are caused by up-regulation of tissue factor which induces coagulation, and by inhibition of fibrinolysis by plasminogen activator inhibitor 1 (PAI-1). Effective antibiotic treatment results in a rapid decline of plasma LPS (half-life 1—3 h) and cytokines, and reduced generation of thrombin, and PAI-1. Early antibiotic treatment is mandatory. Three intervention trials to block lipid A have not significantly reduced the mortality of meningococcal septicemia.
IL-1 regulates in vivo C—X—C chemokine induction and neutrophil sequestration following endotoxemia
Authors: Calkins Casey M. , Bensard Denis D. , Shames Brian D. , Pulido Edward J. , Abraham Edward , Fernandez Nathan , Xianzhong Meng  , Dinarello Charles A. , McIntyre Robert C.
Published: June 2007

The influx of neutrophils into tissues in response to inflammatory stimuli involves C—X—C chemokines. Interleukin-1 (IL-1) stimulates chemokine production in vitro , but its role in vivo on chemokine production is not as clearly understood. We hypothesized that IL-1 mediates in vivo tissue C—X—C chemokine production induced by systemic lipopolysaccharide (LPS). IL-1 activity was blockedbyIL-1 receptor antagonist (IL-1Ra). Rats were injected with Salmonella typhi LPS (0.5 mg/kg) with and without prior administration of IL-1Ra. Cytokine-induced neutrophil chemoattractant-1 (CINC-1) and macrophage inflammatory protein-2 (MIP-2) protein and mRNA levels, tissue neutrophil accumulation, and indices of organ injury were measured. LPS administration resulted in increased plasma, lung, and liver IL-1β that was decreased by IL-1Ra. LPS also induced an increase in plasma, lung, and liver CINC-1 and MIP-2 protein and mRNA. However, IL-1Ra had no effect on LPS-induced plasma or lung tissue CINC-1 levels. In contrast, IL-1Ra pretreatment did significantly decrease CINC-1 protein expression in the liver (45% decrease) and MIP-2 protein expression in plasma (100% decrease), lung (72% decrease) and liver (100% decrease) compared to LPS-treated controls. Steady-state mRNA levels by Northern blot analysis of both CINC-1 and MIP-2 in lung and liver were similar to the protein findings. Pretreatment with IL-1Ra also resulted in a 47% and 59% decrease in lung and liver neutrophil accumulation, respectively, following LPS. In addition, indices of both lung and liver injury were decreased in animals pretreated with IL-1Ra. In summary, LPS induces IL-1β and MIP-2 expression in the lung and liver, both of which are IL-1 dependent. Although lung neutrophil accumulation in both lung and liver after LPS is also IL-1 mediated, lung CINC-1 levels were unaffected by IL-1Ra. These data suggest that IL-1 regulates tissue chemokine expression and neutrophil accumulation after LPS.
Protective effects of isohelenin, an inhibitor of nuclear factor κB, in endotoxic shock in rats
Authors: Sheehan M. , Wong H.R. , Hake P.W. , Zingarelli B.
Published: June 2007

Recent in vitro studies have shown that isohelenin, a sesquiterpene lactone, inhibits the NF-κB pathway. This study examines the effect of isoheleninin endotoxic shock induced by administration of Escherichia coli endotoxini n male Wistar rats. A group of rats received isohelenin (2 mg/kg intraperitoneally)15 min before endotoxin. In vehicle-treated rats, administration of endotoxin caused severe hypotension, which was associated with a marked hyporeactivity to norepinephrine and acetylcholine in ex vivo aortas. Elevated levels of plasma nitrate/nitrite, metabolites of nitric oxide (NO), were also found. These inflammatory events were preceded by cytosolic degradation of inhibitor-κBα (IκBα) and activation of nuclear factor-κB (NF-κB) in the lung within 15 min of endotoxin administration. Treatment with isohelenin resulted in hemodynamicimprovement and reduced plasma levels of NO metabolites. Nuclear translocation of NF-κB was inhibited by isohelenin treatment in the lung, whereas degradation of IκBα was unchanged. In a separate set of experiments, treatment with isohelenin significantly improved survival in mice challenged with endotoxin. We conclude that isohelenin exerts beneficial therapeutic effects during endotoxic shock through inhibition of NF-κB.
Pretreatment with troglitazone decreases lethality during endotoxemia in mice
Authors: Reynolds Karen , Novosad Bo , Hoffhines Adam , Gipson Jenny , Johnson Jared , Peters Jeffrey , Gonzalez Frank , Gimble Jeffrey , Hill Molly
Published: June 2007

Troglitazone is an oral antidiabetic drug that is a ligand for peroxisome proliferator activated receptor γ (PPARγ). Based on other studies that have implicated an immunosuppressive role for PPARγ during inflammatory responses, we hypothesized that troglitazone treatment would improve survival in a murine model of endotoxemia and that the protective effect would be mediated by decreased expression of inflammatory mediators. C57Bl/6N x Sv/129 (wild-type [WT]) or PPARα null mice treated for 2 weeks with dietary troglitazone (0.1%) had significantly fewer deaths and a higher LD 50 value compared to control-fed mice when challenged with lipopolysaccharide (LPS). PPARα null mice were more sensitive to the lethal effects of LPS as evidenced by a 2-fold lower LD 50 (6.6 mg/kg) compared to WT mice (14.6 mg/kg). Troglitazone treatment had no significant effect on LPS-induced plasma TNF, glucose, or nitric oxide levels in WT or PPARα null mice at any of the time points examined. However, troglitazone treatment significantly reduced LPS-induced plasma IL-6 levels in both WT and PPARα null mice. The results of these studies suggest that troglitazone treatment protects mice against a lethal challenge of LPS, but whether or not this effect is mediated through decreased expression of inflammatory mediators remains unclear.
Recognition of lipopeptides by Toll-like receptors
Authors: Takeda Kiyoshi , Takeuchi Osamu , Akira Shizuo
Published: June 2007

Toll-like receptors (TLRs) recognize specific molecular patterns present only in micro-organisms and thereby activate innate immune cells. TLR2 is essential for the recognition of peptidoglycan and lipoprotein/lipopeptides. Lipoprotein/lipopeptides are observed in cell walls of a variety of micro-organisms. Host immune cells recognize the specific patterns of lipoprotein/lipopeptides through the association of TLR2 with other TLRs. TLR1 and TLR6 are highly homologous to TLR2 in structure. TLR6-deficient mice showed an impaired response to mycoplasmal lipopeptides that are diacylated, whereas TLR1-deficient mice were defective in their response to bacterial lipopeptides that are triacylated. TLR2-deficient mice did not show any inflammatory response to either type of lipopeptide. The functional association of TLR2 with TLR1 or TLR6 has been demonstrated. Thus, TLR1 and TLR6 are involved in the discrimination of a subtle difference between triacyl and diacyl lipopeptides through interaction with TLR2.
Innate immune responses in oral mucosa
Authors: Sugawara Shunji , Uehara Akiko , Tamai Riyoko , Takada Haruhiko
Published: June 2007

It is speculated that more than 400 bacterial species reside in the oral cavity. Some cause inflammation ( e.g. periodontitis), understanding of which requires examination of innate immunity in the oral cavity. Oral mucosal cells such as epithelial cells are thought to act as a physical barrier against the invasion of pathogenic organisms, but they have an ability to produce inflammatory cytokines and express adhesion molecules. Oral epithelial cells are refractory to many bacterial components although they express Toll-like receptors/MyD88, and acquire responsiveness after priming with IFN- . When the cells are stimulated with lipopolysaccharide (LPS) and neutrophil protease (PR3) after IFN- priming, the cells produce bio-active IL-18, which is critical to Th1 and Th2 responses. PR3 itself is able to activate the cells through G protein-coupled protease-activated receptor-2 on the cell surface. These results suggest that innate immune responses of oral epithelial cells to bacterial components are regulated in the inflammatory process. In addition, saliva contains abundant bio-active CD14 from salivary glands in a soluble form, although LPS-binding protein was below detectable levels, suggesting that saliva CD14 is important for the maintenance of oral health.
HMGB1 as a cytokine and therapeutic target
Authors: Huan Yang  , Haichao Wang  , Czura Christopher J. , Tracey Kevin J.
Published: June 2007

HMGB1 is an abundant nuclear and cytoplasmic protein present in mammalian cells. It is traditionally known as a DNA binding protein involved in maintenance of nucleosome structure and regulation of gene transcription. Beyond these intracellular roles, we recently discovered that HMGB1 is released from activated macrophages and functions as a late mediator of lethal endotoxemia. Addition of HMGB1 to macrophage cultures activates cytokine release. When released into the extracellular milieu, HMGB1 causes systemic inflammatory responses including acute lung injury, epithelial barrier dysfunction, and death. Passive immunization with anti-HMGB1 antibodies confers significant protection against lethality induced by LPS administration and sepsis caused by cecal perforation in mice. Truncation of HMGB1 into individual structural domains revealed that the HMGB1 A box, a DNA-binding motif, specifically antagonizes the activity of HMGB1 and rescues mice from lethal sepsis caused by cecal perforation. Thus, strategies that target HMGB1 with specific antibodies or antagonists have potential for treating lethal systemic inflammatory diseases characterized by excessive HMGB1 release.
Review: Antimicrobial and immunoregulatory functions of lactoferrin and its potential therapeutic application
Authors: Caccavo Domenico , Pellegrino Nelly M. , Altamura Maria , Rigon Amelia , Amati Luigi , Amoroso Antonio , Jirillo Emilio
Published: June 2007

Lactoferrin is an iron-binding glycoprotein present in various secretions ( e.g. milk, tears, saliva, pancreatic juice, etc.). It is also stored in specific granules of polymorphonuclear granulocytes from which it is released following activation. Lactoferrin exerts a bactericidal activity by damagingthe outer membrane of Gram-negative bacteria, as well as immunoregulatory functions by decreasing the release of interleukin-1 (IL-1), IL-2 and tumor necrosis factor- (TNF-) and enhancing monocyte and natural killer cell cytotoxicity. Lactoferrin binds with high affinity to lipid A, the toxic moiety of the lipopolysaccharide, or endotoxin from Gram-negative bacteria. Lipopolysaccharide interaction with monocytes/macrophages results in the production and release of TNF- , that plays an important role in inducing septic shock. In this respect, it has recently been demonstrated that lactoferrin inhibits the lipopolysaccharide interaction with CD14 on monocytes/macrophages by competition with the lipopolysaccharide binding protein. Therefore, besides its bactericidal activity, lactoferrin may also act by neutralizing the toxic effects of lipopolysaccharide and this protective role against endotoxin lethal shock has been demonstrated in animal models. Moreover, in vitro and in vivo neutralization of endotoxin by a human lactoferrin-derived peptide was also reported and lactoferrin or lactoferrin-derived peptides could represent useful tools for the treatment of endotoxin-induced septic shock. The recent production and characterization of monoclonal antibodies against different epitopes of human lactoferrin, including monoclonal antibodies selectively neutralizinglactoferrin binding to lipid A, may allow a better elucidation of the consequence of lactoferrin-lipopolysaccharideinteraction.
Implication of G i proteins and Src tyrosine kinases in endotoxin-induced signal transduction events and mediator production
Authors: Ferlito Marcella , Romanenko Olga G. , Guyton Kelly , Ashton Sarah , Squadrito Francesco , Halushka Perry V. , Cook James A.
Published: June 2007

Previous studies have suggested that heterotrimeric G proteins and tyrosine kinases may be involved in lipopolysaccharide (LPS) signaling events. Signal transduction pathways activated by LPS were examined in human promonocytic THP-1 cells. We hypothesized that Gi proteins and Src tyrosine kinase differentially affect mitogen-activated protein (MAP) kinases (MAPK) and nuclear factor kappa (NF- B) activation. Post-receptor coupling to G i proteins were examined using pertussis toxin (PTx), which inhibits G i receptor-coupling. The involvement of the Src family of tyrosine kinases was examined using the selective Src tyrosine kinase inhibitor pyrazolopyrimidine-2 (PP2). Pretreatment of THP-1 cells with PTx attenuated LPS-induced activation of c-Jun-N-terminal kinase (JNK) and p38 kinase, and production of tumor necrosis factor-alpha (TNF-) and thromboxane B2 (TxB2). Pretreatment with PP2 inhibited TNF- and TxB2 production, but had no effect on p38 kinase or JNK signaling. Therefore, the G i-coupled signaling pathways and Src tyrosine kinase-coupled signaling pathways are necessary for LPS-induced TNF- and TxB2 production, but differ in their effects on MAPK activation. Neither PTx nor PP2 inhibited LPS-induced activation of interleukin receptor activated kinase (IRAK) or inhibitedtranslocation of NF- B. However, PP2 inhibitedLPS-inducedNF-B transactivation of a luciferase reporter gene construct in a concentration-dependent manner. Thus, LPS induction of Src tyrosine kinases may be essential in downstream NF- B transactivation of genes following DNA binding. PTx had no effect on NF- B activation of the reporter construct. These data suggest upstream divergence in signaling through G i pathways leading to MAPK activation and other signaling events leading to I B degradation and NF- B DNA binding.
Lipopolysaccharide from Rhodobacter sphaeroides is an agonist in equine cells
Authors: Lohmann Katharina L. , Vandenplas Michel , Barton Michelle H. , Moore James N.
Published: June 2007

Endotoxemia is associated with the principal causes of death in adult horses and equine neonates and, therefore, veterinary researchers are expending efforts to identify new therapeutic interventions that might be beneficial in these animals. Endotoxin antagonists inhibit interaction of endotoxin with cellular receptors and may be beneficial in the treatment of endotoxemia and sepsis. Diphosphoryl lipid A from Rhodobacter sphaeroides ( RsDPLA) is a potent antagonist of enteric LPS in human cells, but is an agonist in hamster cells. In this study, the effect of lipopolysaccharide from R. sphaeroides ( RsLPS) on equine whole blood and isolated monocyte preparations was investigated by comparing tumor necrosis factor (TNF) production in response to RsLPS and Escherichia coli O55:B5 LPS. Our results indicate that RsLPS is a potent agonist in equine cells, which precludes therapeutic use of this agent in equine patients. In contrast to the results in equine cells, RsLPS did not elicit TNF production by itself, and inhibited the response to E. coli O55:B5 LPS in a human monocytic cell line.