bluuebunny/crossref_metadata_2025 huggingface dataset:
Damage‐induced changes in woody plants and their effects on insect herbivore performance: a meta‐analysis
Authors: Nykänen Heli , Koricheva Julia
Published: January 2004

We conducted a meta‐analysis of 68 studies published between 1982 and 2000 in which the responses of woody plants to natural or simulated herbivore damage and/or insect herbivore performance on control and damaged plants were measured. Cumulative meta‐analyses revealed dramatic temporal changes in the magnitude and direction of the plant and herbivore responses reported during the last two decades. Studies conducted in the 1980s reported increase in phenolic concentrations, reduction in nutrient concentrations and negative effect on herbivore performance, consistently with the idea of induced resistance. In contrast, in the early 1990s when the idea that some types of plant damage may result in induced susceptibility was generally accepted, studies reported non‐significant results or induced susceptibility, and smaller effects on herbivores. The above changes may reflect paradigm shifts in the theory of induced defenses and/or the differences between study systems used in the early and the more recent studies. Overall, plant growth and carbohydrate concentrations were reduced in damaged plants despite enhanced photosynthetic rates. Damage increased the concentrations of carbon and phenolics, while terpene concentrations tended to decrease after damage; changes in nutrient concentrations after damage varied according to nutrient mobility, inherent plant growth rate, ontogenetic stage and plant type (deciduous/evergreen). Early season damage caused more pronounced changes in plants than late season damage, which is in accordance with the assumption that vigorously growing foliage has a greater capacity to respond to damage. Insect growth rate and female pupal weight decreased on previously damaged plants, while herbivore survival, consumption and male pupal weight were not significantly affected. The magnitude and direction of herbivore responses depended on the type of plant, the type of damage, the time interval between the damage and insect feeding (rapid/delayed induced resistance), and the timing of the damage.
Variation in birch bark secondary chemistry between and within clones: implications for herbivory by hares
Authors: Laitinen M.‐L. , Julkunen‐Tiitto R. , Yamaji K. , Heinonen J. , Rousi M.
Published: January 2004

We studied the variation in bark chemistry between and within 19 European white birch (Betula pendula) clones and its implications to resistance to the mountain hare (Lepus timidus). We used one‐year‐old clonal plantlets originating from randomly selected naturally regenerated parental trees. The same clones were used in both chemical analyses and in feeding experiments. The condensed tannins were analysed by an acid butanol assay, other phenolic components by HPLC‐DAD, and triterpenoid components by HPLC‐MS. The resistance to hare was tested in open‐field feeding experiment. The main phenolic compounds in birch bark were catechin derivatives, rhododendrin, platyphylloside, and condensed tannins, and the main triterpenoids were papyriferic acid and pendulic acid. Most of the variation in the concentrations of the studied compounds was found between clones for the studied phenolics and large variation for triterpenoid components were found both between clones and among plantlets within the same clone. Hares clearly selected among the studied clones. Our results suggest that birch bark chemistry play an important role in resistance to herbivory by hare. The total triterpenoids and total flavonoid‐aglycones showed significant negative correlation with hare feeding. It seems that a genetic basis for bark chemistry and birch resistance is strong. Such a high variation in secondary chemistry both between clones and within individual clones indicates that European white birch populations have a good resistance towards variable environmental conditions and varying pressures from herbivory.
A multivariate search for pollination syndromes among penstemons
Authors: Wilson Paul , Castellanos Maria Clara , Hogue James N. , Thomson James D. , Armbruster W. Scott
Published: January 2004

The seeming ubiquity of spatio‐temporal variation in pollination regime suggests that flowers ought to be adapted to a wide range of pollinators, yet many comparative biologists perceive that in groups with complex flowers there is considerable specialization onto pollination syndromes. Statistical documentation of such syndromes has been presented for very few groups of flowers. Accordingly, we measured, for 49 species of Penstemon and close relatives, both the morphology of the flowers and visitation by pollinators. We describe the mechanics of pollination for representative species. Ordinations show a distinct difference between hummingbird‐pollinated species and hymenopteran‐pollinated species. Flower color is particularly good at separating hummingbird‐ from hymenopteran‐flowers. Other characters are also correlated with this dichotomy. Within the hymenopteran‐pollinated species, there are additional relationships between floral morphology and the size of the principal pollinators. Flowers frequented by large bees, such as Xylocopa, have large open vestibules and relatively short floral tubes. Flowers frequented by smaller bees, such as Osmia, have long narrow floral tubes. Unlike nectar‐collecting bees, pollen‐collecting bees tend to be attracted to flowers of the hummingbird syndrome. The overarching pattern was that syndrome characterizations were successful at predicting pollination by hummingbirds versus Hymenoptera, two types of animals that are profoundly different, but less successful at predicting visitation by one kind of bee versus another.
Metapopulation viability analysis of the bog fritillary butterfly using RAMAS/GIS
Authors: Schtickzelle Nicolas , Baguette Michel
Published: January 2004

Many species living in man‐shaped landscapes are restricted to small natural habitat patches and form metapopulations; predicting their future is a central issue in applied ecology. We examined the viability of the bog fritillary butterflyProclossiana eunomiaEsper, a specialist glacial relict species, in a highly fragmented landscape (<1% of suitable habitat in 10 km2), by way of population viability analysis. We used comprehensive data from a long‐term study in which a patchy population was monitored during ten consecutive years to parameterise a spatially structured metapopulation model using commercially available platform RAMAS/GIS 3.0. Population growth rate was density‐dependent and modulated by various climatic variables acting on different developmental stages of the butterfly. Density dependence was probably related to larval parasitism by a specific parasitoid. Population size was negatively affected by an increase in the mean temperature. Dispersal was modelled as the observed proportion of movements between patches, taking into account the probability of emigration out of a given patch. Our model provided results close to the picture of the system drawn from the field data and was considered as useful in making predictions about the metapopulation. Demographic parameters proved to have a far higher impact on metapopulation persistence than dispersal or correlation of local dynamics. Scenarios simulating both global warming and management of habitat patches by rustic herbivore grazing indicated a decrease in the viability of the metapopulation. Our results prompted the regional nature conservation agency to modify the planned management regime. We urge conservation biologists to use structured population models including local population dynamics for viability analysis targeted to such threatened metapopulations in highly fragmented landscapes.
Immune response and survival
Authors: Møller Anders Pape , Saino Nicola
Published: January 2004

Immune responses have evolved to defend hosts efficiently against the debilitating effects of parasites on host fitness. However, there are relatively few studies of the efficiency of the immune system in terms of providing hosts with an ability to defend themselves against parasitism. A meta‐analysis of the literature on survival of birds in relation to non‐specific immune response to challenge with an antigen or other measures of immune function demonstrated a mean effect adjusted for sample size of 0.43 across 12 studies. This observation shows that relatively simple estimates of non‐specific immune responses often reliably predict a large and significant amount of variation in survivorship.
Mate limited reproductive success in two dioicous mosses
Authors: Bisang Irene , Ehrlén Johan , Hedenäs Lars
Published: January 2004

We tested whether mate availability in the pleurocarpous dioicous mosses Rhytidiadelphus triquetrus and Abietinella abietina affects fertilization success by transplanting individual male shoots into non‐sporophytic female colonies. Fertilization success in both species was limited by the availability of mates and distance‐dependent, and the number of sporophytes produced was higher in R. triquetrus than in A. abietina. Our estimate of a maximum fertilization distance of 34 cm in R. triquetrus is an order of magnitude larger than previous estimates that have been based on non‐manipulative approaches. In R. triquetrus the number of female reproductive branches and plot inclination (horizontal vs sloping) had significant effects on the number of sporophytes produced. In A. abietina, the number of female reproductive branches per plot did not affect sporophyte production. Within sloping experimental plots, sporophyte number was significantly higher, and the distance of sporophytes from the spermatozoid source was larger below the male transplants than above. We conclude that mate availability may be important for reproductive success in sessile dioecious organisms, and that the spatial structure at various scales is essential to understand their dynamics.
Specificity of induced plant responses to specialist herbivores of the common milkweed Asclepias syriaca
Authors: Van Zandt Peter A. , Agrawal Anurag A.
Published: January 2004

Induced plant responses to herbivory appear to be universal, yet the degree to which they are specific to sets of herbivores is poorly understood. The generalist/specialist hypothesis predicts that generalist herbivores are more often negatively affected by host plant defenses, wheras specialists may be either unaffected by or attracted to these same “plant defenses”. Therefore, specialists should be less predictable than generalists in their responses to induced plant resistance traits. To better understand the variation in plant responses to herbivore attack, and the impacts these responses have on specialist herbivores, we conducted a series of experiments examining pairwise interactinos between two specialaist herbivores of the common milkweed (Asclepias syriaca). We damaged plants mechnically, with swamp milkweed beetles (Labidomera clivicollis), or with monarchs (Danaus plexippus), and then asessed specificity of elicitation, both by measuring a putative defensive trait (latex volume) and by challenging plants with insects of both species in bioasays. Latex production increased by 34% and 13% following beetle and monarch herbivory, respectively, but only beetles significantly elevated latex production compared to undamaged controls. While beetle growth was negatively affected by latex across all experiments, beetles were not affected by previous damage caused by conspecifies or by monarchs. In contrast, monarchs feeding on previously damaged plants were 20% smaller, and their response was the same on plants damaged mechnically or by either herbivore. Therefore, these specialist herbivores exhibit both specificity of elicitation in plant responses and specificity of effects in response to prior damage.
Collecting French seventeenth‐century paintings for the nation
Authors: Pace Claire
Published: January 2004

National Gallery Catalogues: the 17th‐century French Paintings by Humphrey Wine, London: The National Gallery, 2001, 438 pp., 106 col. plates, 266 b. & w. illus., £50.00
How Romney was framed
Authors: Alfrey Penelope
Published: January 2004

George Romney 1734‐1802 by Alex Kidson, London: National Portrait Gallery, 2002, 256 pp., 146 col. plates, 70 b. & w. illus., £40.00

Those Delightful Regions of Imagination: Essays on George Romney edited by Alex Kidson, Studies in British Art 9, New Haven & London: Yale University Press, 2002, 288 pp. 8 col. plates, 118 b. & w. illus., £35.00
L'age d'or‐dinaire: a voyage through Surrealism
Authors: Allmer Patricia
Published: January 2004

History of the Surrealist Movement by Gérard Durozoi, translated by Alison Anderson, London: University of Chicago Press, 2002, 816 pp., 232 col. plates, 777 halftone illus., £60.00
It's not only art
Authors: Radford Robert
Published: January 2004

The Battle For Realism: Figurative Art in Britain During the Cold War 1945–1960 by James Hyman, Yale University Press, for The Paul Mellon Centre for Studies in British Art, 2001, 264 pp., 24 col. plates, 148 b. & w. illus., £45.
Fascinated by Fog
Authors: Beslshaw Michael , Beslshaw Michael
Published: January 2004

Conceptual Art and Painting: Further Essays on Art & Language by Charles Harrison, Cambridge, Mass.: the MIT Press, 2001, 234 pp., 90 b. & w. illus., £23.95
A Rebellious Collection
Authors: Gane Mike
Published: January 2004

Impossible Presence: Surface and Screen in the Photogenic Era, edited by Terry Smith, Chicago: University of Chicago Press, 2001, 300 pp., £15.50
The Grace of Time: narrativity, sexuality and a visual encounter in the Virtual Feminist Museum
Authors: Pollock Griselda
Published: January 2004

This paper is part of a larger project exploring the concept of a Virtual Feminist Museum through the relations of time, space and the archive. Feminist analysis needs to take on the manner in which the history of images is conserved and presented through museum display and the curatorial mode that informs art‐historical study by master, image, style and period. To track the political unconscious of the image with all its ambivalence, the essay draws on Freudian aesthetics in the study of a photographic archive of fragments and details of Antonio Canova's Three Graces, which are set against a counter‐archive of work by artists who are women exploring bodies, sexuality and time.
Who knows where the sublime goes?
Authors: Souza Pauline de
Published: January 2004

Sticky Sublime edited by Bill Beckley, New York: Allworth Press, 2001, 269pp., 14 b. & w. illus., £18.95

Death's Showcase by Ariella Azoulay, translated by Ruvil Daniell, Massachusetts Institute of Technology Press, 2001, 303pp., 000 b. & w. illus., £23.95
The Problem with Looking at Pieter Bruegel's Elck
Authors: Rothstein Bret
Published: January 2004

This essay concerns optical wit in Pieter Bruegel's Elck (1558). While scholars have treated this print as an earnest essay in human frailty, I focus instead on its playful negations both of knowledge and of one who would possess it. Building on Peter Parshall's earlier delineation of this paradoxical theme, I suggest that Elck uses a parallelism based in looking to implicate the viewer as one who would obtain a measure of understanding from, or apply it to, the printed image: as the protagonist Elck (Everyone) pores over worldly goods, and as his counterpart Niemant (Nobody) gazes foolishly into a mirror, so does the viewer assess the print. All look, but few – if any – truly see. The implications of this parallelism are crucial. The successful (that is, knowledgeable) interpreter must necessarily cease to exist, as knowledge is, according to the print, the sole province of Nobody; the other option, interpretive failure, associates us with Everyone, who patently lacks any knowledge whatsoever. Bruegel thus cleverly indicts the interpretive skills of his audience by denying the potential for anything but nonsensical reading. I suggest that the print thus disrupts traditional responses to the image and, consequently, calls into question the relationship between artist, object, and observer.
Max Dvořák: art history and the crisis of modernity
Authors: Rampley Matthew
Published: January 2004

The work of Max Dvořák has seldom enjoyed the acclaim accorded to that of his Viennese colleague Alois Riegl, or contemporaries such as Aby Warburg and Heinrich Wölfflin. This paper argues for a reconsideration of his work, in which his ‘art history as the history of ideas’ is seen both as a lens through which Dvořák conducted a sustained commentary on the present, and also as a critique of modernity comparable to the social and economic theories of Ernst Troeltsch, Ferdinand Tönnies, Georg Simmel or Ernst Mach. The article argues that Dvořák's work offers an important example of the numerous intellectual and political tensions at work in the final years of the Habsburg monarchy. As such, the article aims to question the institutional frame within which much art‐historical writing is often analysed.
Introduction: Visibility, Difference and Excess
Authors: Perry Gill
Published: January 2004

This introductory essay explores some of the complexities and ambiguities which underpin a concept of ‘difference’ in the production and interpretation of recent art. Issues within the current discourse on gender and ‘women's art’ are considered, including concerns with cultural, curatorial and psychic mechanisms of in/visibility, with an emphasis on developments in British art. The essay examines some of the institutional and cultural reasons for the increasing visibility of work by (some) British women artists, while also seeking to problematize the notion of ‘Britishness’. By mapping out the range of subjects (including American and Irish artists), and strategies of interpretation included in this collection, the introduction suggests ways in which gender and ethnicity might figure in an exploration of ‘difference’ in contemporary art theory and practice.
A Strange Alchemy: Cornelia Parker
Authors: Tickner Lisa
Published: January 2004

Cornelia Parker was nominated for the Turner Prize in 1997 and has exhibited widely in Britain, Europe and America, including a solo exhibition at the Serpentine Gallery in 1998. In conversation with Lisa Tickner, she discusses the impact of her early training and explores in detail sculptures and installations produced and exhibited since 1989. These include Thirty Pieces of Silver (1998), Cold Dark Matter: An Exploded View (1991) and The Maybe (1995). Parker discusses these works with reference to her fascination with particular materials, working processes and sculptural transformations.
Antibodies: Rachel Whiteread's Water Tower
Authors: Malvern Sue
Published: January 2004

First commissioned in 1994 and installed on a rooftop in SoHo, New York City, in 1998, Rachel Whiteread's Water Tower has been described with tropes identifying it as an alien presence on the New York skyline. In effect, Water Tower– and, by extension, the artist herself – has been classed as an immigrant or a foreign body, marked by difference. Water Tower is a tour de force of resin casting from one of New York's unique and ubiquitous wooden water towers, and has also been seen as a monument or a memorial. The piece was recently purchased and donated to the Museum of Modern Art, New York, and a once‐discreet, sometimes invisible, ephemeral sight, that played on presence and absence, became a permanent monument in the canon of modern art.
Reading Black Through White in the Work of Kara Walker
Authors: Corris Michael , Hobbs Robert
Published: January 2004

The work of the American artist Kara Walker is simultaneously celebrated as a potent allegory on the state of race relations in the US and reviled for its use of blatant racial stereotyping that harkens back to the era of slavery in the ante‐bellum South. In a staged dialogue aimed at addressing the terms of the controversy surrounding Walker, the authors explore the subtleties and contradictions of the artist's approach by examining, amongst other examples, the origins and significance of the large‐scale panorama Slavery, Slavery (1997).
Corporeal Theory with/in Practice: Christine Borland's Winter Garden
Authors: Meskimmon Marsha
Published: January 2004

Focusing on the work Winter Garden, produced in 2001 by Scottish artist Christine Borland, the essay argues that contemporary women's art can move beyond the idea of the body as an object to interrogate sexual difference as a process of the ‘in‐between’. Winter Garden can be seen to materialize concepts and enfold ‘theory’ with/in ‘practice’ in a vital, corporeal exchange with bodies in the world. This fact invites feminist art critics and historians to engage artwork otherwise. The essay suggests that this engagement is both mobile and located: a resonant critical practice takes theory as corporeal, part of a mutual knowledge project, itself capable of creative change and development in its encounter with different images, objects and ideas. Thinking through Winter Garden, some of the implications of corporeal theory are explored as forms of inventive feminist thought.
Cultural Crossings: performing race and transgender in the work of moti roti
Authors: Rowe Dorothy
Published: January 2004

This essay investigates the possibilities offered for an exploration of racial and gendered identities as performed through the experimental art projects of the diasporic London‐based artist‐led group moti roti. Framed within the context of a Butlerian theory of the performative, moti roti's 1995 installation/performance, Wigs of Wonderment is considered both in terms of Butler's proposition for the destablization of fixed gendered identities and sexual identifications, but also in terms of Homi Bhaba's incisive analysis of the rigidity of terms through which colonial discourse maintains its authority. Dislodging racial, sexual and gendered categories through the introduction of third term (the cross‐dresser, the hybrid), dependent for its disruptive effects of difference and excess upon the power of parodic imitation and mimicry, Wigs of Wonderment exposes the instability of identification with sensuality, empathy and frequent humour.
‘South Opposed to East and North’: Adrian Stokes and Josef Strzygowski. A study in the aesthetics and historiography of Orientalism
Authors: Kite Stephen
Published: January 2004

The ‘South Opposed to East and North’ of this paper's title comes from the third section of Adrian Stokes's book The Quattro Cento of 1932 – subtitled A Different Conception of the Italian Renaissance, and the founding work of his aesthetic. The Quattro Cento can be viewed as a response to the need expressed by Strzygowski in his Origin of Christian Church Art of 1923 ‘for a work dealing with the penetration of the South by the North of Europe and the subsequent rise of the so‐called Renaissance’; a North, in Strzygowski's view, already permeated by influences from the East. Within the contested terrain inscribed in the term, this paper isolates three key ‘Orients’ crucial to Stokes's Quattro Cento aesthetic: the experiential Orient of his Conrad‐inspired voyage to the East; the Orient of the British Museum; and that of the Orientalist texts – primarily the now‐marginalized Josef Strzygowski. As a study in the historiography of Orientalism, the essay examines how Adrian Stokes inflected his experience and readings of these Orients to re‐evaluate European – specifically Italian Renaissance – culture.
Transatlantic Cultural Politics in the late 1950s: the Leaders and Specialists Grant Program
Authors: Jachec Nancy
Published: January 2004

Using recently declassified US State Department documents from the Leaders and Specialists Grant Program (LSGP), this article examines American Abstract Expressionism's success in Western Europe within the context of Euro‐American foreign policy, and specifically the promotion of the European Union in the late 1950s. Our current understanding of the politics of Abstract Expressionism tends to assume that Europeans were passive in the face of American cultural expansion, as well as to overlook the specific policy objectives that may have been pursued by the individuals and governments involved in the international cultural exchanges which yielded the exhibitions Jackson Pollock 1912–1956 and The New American Painting, which are widely held to mark the emergence of a world‐class American culture. This article argues that the success of these shows was in fact the result of the efforts of European and American cultural figures involved in the LSGP, an educational exchange programme administered by the State Department and working through the pro‐American European Movement to promote gesture painting as an Atlanticist cultural practice.
The Living City Survival Kit: a portrait of the architect as a young man
Authors: Sadler Simon
Published: January 2004

This article discusses an image published on the occasion of the Living City exhibition held at the Institute of Contemporary Arts, London, in 1963. The image, here referred to as Living City Survival Kit, is ascribed to Warren Chalk, and it was produced within the milieu of the Archigram group. In a manner akin to Pop Art, the image represents the modernization of everyday life. Unlike Pop Art, it is about architecture; and unlike traditional architectural images, this image contains no buildings. Instead, the image draws attention to the invisible complement of architecture – how it is used, and how it shapes the experience of the user. The architect, it appears, can no longer impose legitimate order, nor claim genderless, objective distance from the subject of architecture. The image is ultimately concerned with the construction of the architect himself, to the point that it can be read as a self‐portrait.
NASEN/TES Academic Book Award 2003
Authors: Thomas Gary
Published: January 2004

Girts and Exclusion: Rethinking the Agenda

Audrey Osler and Kerry Vincent
Looking out for each other: children helping left‐out children
Authors: Arthur Linet
Published: January 2004

Linet Arthur's article explores an issue of concern to all teachers from time to time, no matter what the age group they teach. It is refreshing, therefore, to read this study of a project carried out in a group of primary schools which had a positive impact at all the schools involved. While many articles published in this journal touch on the question of social inclusion for children with special educational needs, we welcome this one which looks at it specifically.
Short‐term projects: the Standards Fund and collaboration between speech and language therapists and teachers
Authors: Wright Jannet A. , Kersner Myra
Published: January 2004

As a strategy in education, short termism has been much criticised. In this article Jannet Wright and Myra Kersner consider the effects of short‐term projects in relation to their own area of expertise in speech and language therapy. While they find such projects encourage creativity they also identify some serious limitations.
Consulting with students: evaluating a mainstream inclusion centre
Authors: Preece Dawn , Timmins Paul
Published: January 2004

The Government Standards Fund made resources available to schools in 2000 to help reduce the number of exclusions and, as a result, many schools established inclusion centres with this purpose in mind. In this article Dawn Preece and Paul Timmins describe literature and research that support the value of these centres and identify features of a support centre that students felt contributed to their inclusion in school. The results of an evaluation canvassing the perceptions of students attending one such centre are presented and discussed.
Analysing the management of challenging behaviour in Romanian orphanages: looking for ways forward
Authors: Hardman Claire
Published: January 2004

In this article Claire Hardman reflects on her work on behaviour management in two Romanian orphanages Quite apart from the intrinsic interest of the topic, the article serves as a reminder of the number of professionals in this country who regularly take time out to work abroad in unfamiliar and often challenging circumstances and who come back with much to contribute to debates at home.
Computer‐Assisted Prediction of HLA‐DR Binding and Experimental Analysis for Human Promiscuous Th1‐Cell Peptides in the 24 kDa Secreted Lipoprotein (LppX) of Mycobacterium tuberculosis
Authors: Al‐Attiyah R. , Mustafa A. S.
Published: January 2004

The secreted 24 kDa lipoprotein (LppX) is an antigen that is specific for Mycobacterium tuberculosis complex and M. leprae. The present study was carried out to identify the promiscuous T helper 1 (Th1)‐cell epitopes of the M. tuberculosis LppX (MT24, Rv2945c) antigen by using 15 overlapping synthetic peptides (25 mers overlapping by 10 residues) covering the sequence of the complete protein. The analysis of Rv2945c sequence for binding to 51 alleles of nine serologically defined HLA‐DR molecules, by using a virtual matrix‐based prediction program (propred), showed that eight of the 15 peptides of Rv2945c were predicted to bind promiscuously to ≥10 alleles from more than or equal to three serologically defined HLA‐DR molecules. The Th1‐cell reactivity of all the peptides was assessed in antigen‐induced proliferation and interferon‐γ (IFN‐γ)‐secretion assays with peripheral blood mononuclear cells (PBMCs) from 37 bacille Calmette–Guérin (BCG)‐vaccinated healthy subjects. The results showed that 17 of the 37 donors, which represented an HLA‐DR‐heterogeneous group, responded to one or more peptides of Rv2945c in the Th1‐cell assays. Although each peptide stimulated PBMCs from one or more donors in the above assays, the best positive responses (12/17 (71%) responders) were observed with the peptide p14 (aa 196–220). This suggested a highly promiscuous presentation of p14 to Th1 cells. In addition, the sequence of p14 is completely identical among the LppX of M. tuberculosis, M. bovis and M. leprae, which further supports the usefulness of Rv2945c and p14 in the subunit vaccine design against both tuberculosis and leprosy.
Effect of Dendritic Cells on Flow Cytometric Quantification of Cytomegalovirus‐Specific, Interferon‐γ‐Producing T Cells
Authors: Fleischer C. C. , Solling C. , Petersen M. S. , Agger R. , Hokland M. E.
Published: January 2004

Flow cytometric measurement of intracellular cytokines in T cells exposed to antigen is a widely used method for quantification of an antigen‐specific T‐cell response. As the frequency of antigen‐specific T cells is often very low, any improvement in signal to noise ratio is of great importance. Thus, in this study, the ability of antigen‐pulsed dendritic cells (DCs) to increase the number of antigen‐specific, interferon‐γ (IFN‐γ)‐producing CD4+ T cells measurable both in fresh peripheral blood and in reconstituted frozen blood mononuclear cell (MNC) samples was evaluated. Cytomegalovirus (CMV) was used as antigen in a 10 h assay, using cells from both CMV‐seropositive and ‐seronegative donors. When reconstituted frozen samples were analysed, the general response towards CMV lysate in CMV‐seropositive donors was 23–86% lower compared to the corresponding fresh blood samples. Antigen‐pulsed DCs could not improve the sensitivity of the intracellular cytokine‐detection assay when fresh peripheral blood samples were used. Interestingly, however, the addition of CMV lysate‐pulsed DCs to cryopreserved MNC samples substantially increased the frequency of specifically induced IFN‐γ‐producing cells to a level comparable to the frequency found in the corresponding fresh blood samples.
Clinical Association of Anti‐Golgi Autoantibodies and their Autoantigens
Authors: Hong H.‐S. , Chung W. H. , Hung S. I. , Chen M. J. , Lee S. H. , Yang L. C.
Published: January 2004

Anti‐Golgi autoantibodies (AGAs) and their targets have been reported from several diseases. However, the association of AGAs, selective autoantigens and related clinical diseases is still obscure. In this study, the presence of AGAs in the sera of 5983 patients was screened to explore the association of AGAs and clinical diseases. By means of indirect immunofluorescence using HEp‐2 cells, sera of 12 patients bearing AGAs were identified. The location of recognized Golgi autoantigen(s) was confirmed by the treatment of monensin and double immunostaining using β‐COP. Using the immunoelectron microscopy, AGA immunoreactivity was clearly demonstrated at a stack structure, characteristic of the Golgi complex. Furthermore, analysis of the 12 AGA‐positive sera by Western blot revealed at least 15 components of Golgi antigens with relative molecular weights ranging from 54 to 350 kDa, and several Golgi autoantigens identified may be novel. Notably, over half of the AGA‐positive cases found belong to non‐autoimmune diseases, particularly hepatic disorder. This study presents the association of AGAs, components of the Golgi complex and clinical diseases.
Ligation of CD47 During Monocyte Differentiation into Dendritic Cells Results in Reduced Capacity for Interleukin‐12 Production
Authors: Johansson U. , Londei M.
Published: January 2004

We have previously shown that the CD47‐binding thrombospondin‐1 (TSP‐1)‐derived peptide 4N1K induces a rapid apoptosis‐like death of human monocytes and dendritic cells (DCs). However, not all cells were susceptible to the peptide‐induced cell death and here, we have investigated whether surviving monocytes could differentiate into functionally normal DCs. We found that the cell‐surface phenotype, the T‐cell stimulatory capacity and the ability to undergo lipopolysaccharide (LPS)‐induced maturation into CD83+ DCs were essentially identical in 4N1K‐derived and control DCs. Interleukin‐10 (IL‐10) production was also normal, but a significant downregulation of the pro‐inflammatory cytokines IL‐12 and tumour necrosis factor‐α (TNF‐α) was observed in the 4N1K‐derived DCs. To the contrary, simultaneous stimulation of control DCs with 4N1K and LPS + interferon‐γ did not alter IL‐12 production. These results indicate that although activation of the TSP‐1‐binding region of CD47 on monocytes induces apoptosis in a large proportion of the cells, it does not hamper the overall capacity of the surviving cells to differentiate into DCs. Such DCs, however, have a reduced capacity for IL‐12 and TNF‐α production, and the possibility that this is linked to the uptake of apoptotic cells is discussed.
Human Plasma‐Derived Mannose‐Binding Lectin: A Phase I Safety and Pharmacokinetic Study
Authors: Valdimarsson H. , Vikingsdottir T. , Bang P. , Saevarsdottir S. , Gudjonsson J. E. , Oskarsson O. , Christiansen M. , Blou L. , Laursen I. , Koch C.
Published: January 2004

Mannose‐binding lectin (MBL) is an important component of innate immunity that can bind to certain sugar residues on the surface of many types of pathogenic micro‐organisms. On binding, MBL generates opsonic activity mainly through activation of the complement system. Genetically determined MBL deficiency is very common and can be associated with increased susceptibility to a variety of infections, especially in children and immunosuppressed individuals. The potential benefits of MBL reconstitution therapy therefore need to be evaluated. We have carried out a phase I safety and pharmacokinetic study on 20 MBL‐deficient healthy adult volunteers. The MBL was prepared from plasma of nonremunerated, voluntary Danish donors tested and found negative for hepatitis B surface antigen, antibodies to human immunodeficiency virus (HIV) and hepatitis C virus. Each volunteer received a total of 18 mg of MBL in three 6 mg doses given intravenously, once weekly over a period of 3 weeks. The volunteers were closely monitored at the University Hospital in Reykjavik for 8 h after each infusion and daily thereafter for 5 days after each infusion. No adverse clinical or laboratory changes were observed in any of the 20 participants, and frequent measurements did not reveal any signs of infusion‐associated complement activation. No antibodies to MBL, HIV or hepatitis viruses were observed 24 weeks after the last infusion. Serum MBL levels increased up to normal levels (1200–4500 ng/ml) immediately after each infusion, but the half‐life of the infused MBL was highly variable, ranging from 18 to 115 h (mean 69.6). It is concluded that infusion of purified MBL as prepared by Statens Serum Institut (SSI) is safe. However, adults have to be given at least 6 mg twice or thrice weekly for maintaining protective MBL levels assumed to be about 1000 ng/ml.
Immunological Crossreactivity of the Mycobacterium leprae CFP‐10 with its Homologue in Mycobacterium tuberculosis
Authors: Geluk A. , Van Meijgaarden K. E. , Franken K. L. M. C. , Wieles B. , Arend S. M. , Faber W. R. , Naafs B. , Ottenhoff T. H. M.
Published: January 2004

Mycobacterium tuberculosis culture filtrate protein‐10 (CFP‐10) (Rv3874) is considered a promising antigen for the immunodiagnosis of tuberculosis (TB) together with early secreted antigens of M. tuberculosis (ESAT‐6). Both ESAT‐6 and CFP‐10 are encoded by the RD1 region that is deleted from all tested M. bovis bacille Calmette–Guérin (BCG) strains but present in M. leprae, M. tuberculosis, M. bovis, M. kansasii, M. africanum and M. marinum. In this study, the homologue of CFP‐10 in M. leprae (ML0050) is identified and characterized. Interferon‐γ production in response to this homologue by T cells from leprosy patients, TB patients and unexposed controls shows that CFP‐10 of M. leprae is a potent antigen that crossreacts with CFP‐10 of M. tuberculosis at the T‐cell level. This crossreactivity has implications for the use of CFP‐10 of these mycobacterial species as diagnostic tool in areas endemic for both the diseases.
Synthesis and Immunological Activity of a Branched Peptide Carrying the T‐cell Epitope of gp43, the Major Exocellular Antigen of Paracoccidioides brasiliensis
Authors: Taborda C. P. , Nakaie C. R. , Cilli E. M. , Rodrigues E. G. , Silva L. S. , Franco M. F. , Travassos L. R.
Published: January 2004

The 43 kDa glycoprotein (gp43) of Paracoccidioides brasiliensis is the major diagnostic antigen of paracoccidioidomycosis (PCM), a prevalent fungal infection in South America. A 15‐mer sequence from gp43, denominated P10, induced T‐CD4+ T helper 1 cellular immune responses in mice of three different haplotypes and protected against intratracheal challenge by a virulent isolate of P. brasiliensis. In an attempt to improve delivery of P10, a promiscuous antigen also presented by human leucocyte antigen‐DR alleles, aiming at immunotherapy, we synthesized a multiple antigen peptide with the protective T‐cell epitope expressed in a tetravalent 13‐mer analog of P10 (M10). M10 induced specific lymph node cell proliferation in mice preimmunized with peptides in complete Freund's adjuvant (CFA). In addition, M10 immunization without CFA significantly protected intratracheally infected mice. We conclude that M10 is a candidate for an anti‐PCM vaccine. In this report we describe: (1) the synthesis of M10; (2) the induction of M10‐elicited T‐cell response and (3) in vivo protection of mice immunized with M10 and challenged by a virulent strain of P. brasiliensis.
The Effects of Interferon‐α2a on Concentrations of Immunoglobulins, Complement and Lymphocytes in Patients with Multiple Sclerosis
Authors: Ulvestad E. , Aarseth J. H. , Vedeler C. , Nyland H. , Myhr K.‐M.
Published: January 2004

Multiple sclerosis (MS) patients treated with type I interferon experience reduced disease activity. Because immunoglobulins (Igs), complement and lymphocytes have been given a role in the pathogenesis of MS, we investigated the longitudinal effect of interferon‐α2a (IFNA) on the variability of these parameters. Patients were treated for 6 months with 4.5 million international units (MIU) IFNA (24 patients), 9.0 MIU IFNA (21 patients) or placebo (23 patients). IFNA induced a significant increase in concentrations of total IgG and IgG subclasses 1, 3 and 4. At 6 months, the mean concentration of IgG had increased by 1.51 g/l (CI: 0.82, 2.21) in the 9.0 MIU IFNA group. There was no significant effect of IFNA treatment on concentrations of IgG2 and IgA, while the effect on IgM was borderline significant. After 6 months, IgM had increased by 0.29 g/l (CI: −0.01, 0.65) in the 9.0 MIU IFNA group. IFNA induced a significant increase in the concentration of C1 inhibitor (INH). At 3 months, the mean concentration of C1 INH had increased by 0.033 g/l (CI: 0.01, 0.05). At 3 months, C4 had increased by 0.05 g/l (CI: 0.01, 0.09) in the 9.0 MIU IFNA group. The effect of IFNA on C4 was inconclusive but indicates an effect during the initial phase of the treatment. C3 showed no significant treatment‐mediated change. IFNA induced a significant decrease in lymphocyte concentrations by 0.56 × 106 lymphocytes/ml (CI: −0.81, −0.31) at 3 months. There were no significant associations between changes in immune parameters and changes in clinical and magnetic resonance imaging scores. The results verify that IFNA modulates and activates both the innate and the adaptive arms of the immune system. The observations should be of relevance when evaluating mechanisms of action of IFN treatment in MS.
The four mouse IgG isotypes differ extensively in bactericidal and opsonophagocytic activity when reacting with the P1.16 epitope on the outer membrane PorA protein of Neisseria meningitidis
Authors: Michaelsen T. E. , Kolberg J. , Aase A. , Herstad T. K. , Høiby E. A.
Published: January 2004

Mouse monoclonal antibodies (MoAbs) of the four IgG isotypes, all specific for the P1.16 epitope on the meningcoccal PorA protein, were tested for functional activities. The avidities of the antibodies, measured by NH4SCN elution in enzyme‐linked immunosorbent assay, showed similar values for all the MoAbs. The serum bactericidal activity (SBA) defined as the lowest concentration of antibodies giving 50% reduction in the number of meningococcal colony‐forming units using human serum as complement, showed a hierarchy of IgG3 >> IgG2b > IgG2a >> IgG1. For the opsonophagocytosis (OP), the hierarchy was IgG3 > IgG2b = IgG2a >> IgG1. OP was measured in flow cytometry using log‐phase live meningococci as target cells, normal human peripheral blood polymorphonuclear cells (PMNs) as effector cells and human serum as a complement source. The mouse MoAbs were negative in OP when using human PMNs in the absence of complement. The results demonstrate the importance of choosing the right isotype of mouse MoAbs when using them to judge the potential vaccine importance of their corresponding antigen. If such MoAbs should be used for passive vaccination against infectious diseases, the isotype would presumably play an important role for their anticipated clinical effects.
Low Number of H‐2Dd‐Negative Haematopoietic Cells in Mixed Bone Marrow Chimeras Convey In Vivo Tolerance to H‐2Dd‐Negative Cells But Fail to Prevent Resistance to H‐2Dd‐Negative Leukaemia
Authors: Johansson M. H. , Höglund P.
Published: January 2004

Natural killer (NK) cells kill cells lacking self major histocompatibility complex (MHC) class I. This missing self reactivity is beneficial in haploidentical bone marrow transplantations to cure leukaemia, in which donor‐derived NK cells reject MHC disparate leukaemia cells and prevent relapse. To understand the role of NK cells in transplantation, we have studied NK cell tolerance in mice receiving mixed bone marrow transplants with limiting number of the MHC disparate component. Using an MHC class I (Dd) transgenic mouse model, we generated bone marrow chimeras carrying mixtures of Dd‐positive and ‐negative cells. NK reactivity against Dd‐negative cells (missing self) was assayed by outgrowth of lymphoma cells, stability of the chimerism in vivo and killing of Concanavalin A blasts in vitro. Up to 20% Dd‐negative haematopoietic cells reduced, but did not abrogate, rejection of Dd‐negative tumours and killing of Dd‐negative T‐cell blasts. In contrast, the ratios between Dd‐positive and ‐negative cells were stable in vivo, suggesting tolerance to normal cells. Our data suggest that NK cell tolerance to normal cells and tumours in mixed MHC environments is differentially regulated, tolerance to normal cells being more easily induced. These results are important in relation to the role of NK cells in antileukaemic reactions after bone marrow transplantation.
Limited Magnitude and Breadth in the HLA‐A2‐Restricted CD8 T‐Cell Response to Nef in Children with Vertically Acquired HIV‐1 Infection
Authors: Chandwani R. , Jordan K. A. , Shacklett B. L. , Papasavvas E. , Montaner L. J. , Rosenberg M. G. , Nixon D. F. , Sandberg J. K.
Published: January 2004

CD8 T cells are believed to play a key role in the immune control of human immunodeficiency virus‐1 (HIV‐1) infection in children as well as in adults. We have used an enhanced EliSpot (AmpliSpot) assay to quantitate CD8 T‐cell responses directed to five human leucocyte antigen (HLA)‐A2‐presented HIV‐1 epitopes derived from the key viral antigen Nef. Responses were assayed in one group of 21 children with vertically acquired HIV infection and one group of 19 adult subjects with chronic infection. The paediatric group displayed significantly weaker and more narrowly focused CD8 T‐cell responses as compared with the adult subjects. Two epitopes stood out as the most frequently and strongly recognized, suggesting that they should be considered immunodominant in the CD8 T‐cell response to HIV‐1 Nef. Interestingly, the most frequently and strongly recognized epitope in both adults and children was previously identified in HLA‐A2‐transgenic mice, demonstrating the usefulness of such mice in finding natural viral epitopes. These findings indicate significant weakness in strength and breadth of the CD8 T‐cell response to the target protein Nef in infected children and prompt renewed efforts into the immunology of vertically acquired HIV‐1 infection.
Uninvestigated dyspepsia and non‐ulcer dyspepsia—the use of endoscopy and the roles of Helicobacter pylori eradication and antisecretory therapy
Authors: Chey W. D. , Moayyedi P.
Published: January 2004

Due to its prevalence, impact on quality‐of‐life and the associated significant health resource utilization, dyspepsia is a major healthcare concern. The available management strategies for uninvestigated dyspepsia include prompt endoscopy, the ‘test‐and‐treat’ strategy for Helicobacter pylori, and empiric antisecretory therapy. There is consensus that endoscopy should be reserved for patients with alarm features (e.g. symptom onset after 45 years of age, recurrent vomiting, weight loss, dysphagia, evidence of bleeding, anaemia), H. pylori‐positive individuals who fail test‐and‐treat, and those with an inadequate response to empiric antisecretory therapy. Factors influencing the decision between test‐and‐treat and empiric antisecretory therapy in uninvestigated dyspepsia include the local prevalence of H. pylori and peptic ulcer disease and the proportion of ulcers attributable to H. pylori. For uninvestigated dyspepsia in patients without alarm features, test‐and‐treat is the preferred initial management method in Europe based on the relatively high prevalence of H. pylori/peptic ulcer disease whereas empiric antisecretory therapy is preferred in many parts of the United States, where the prevalence of H. pylori/peptic ulcer disease is relatively low. In patients with non‐ulcer dyspepsia, H. pylori eradication and empiric antisecretory therapy result in comparable and small, but statistically significant, improvements in dyspepsia. Empiric antisecretory therapy is the preferred initial method of managing non‐ulcer dyspepsia in Europe and the US. The test‐and‐treat approach would receive increased enthusiasm if H. pylori cure is shown to prevent development of gastric cancer in non‐ulcer dyspepsia patients in a large Western trial.