bluuebunny/crossref_metadata_2025 huggingface dataset:
Determination of the v-j vector correlation in the photodissociation of nitrosobenzene at 305 nm
Authors: Bartz Jeffrey A. , Everhart Stephanie C. , Cline Joseph I.
Published: February 2010

The 305 nm photofragmentation dynamics of nitrosobenzene was measured using velocity-mapped ion imaging with polarized 1+1′ resonance-enhanced multiphoton ionization probing of the NO (X, v″=0) fragment. The product recoil energy and angular distributions of selected rotational states of NO (X Π21/2,3/2) products have been measured. The recoil anisotropy of the NO photofragment is very small with β02(20)=0.03. The v-j vector correlation of NO shows a preference for v∥j with an average value of β00(22)=+0.15 over the transitions studied. A mechanism involving dissociation from the ground state is used to explain the unusual propellerlike trajectory of the nascent NO.
Tunable electrical and optical properties of hafnium nitride thin films
Authors: Farrell I. L. , Reeves R. J. , Preston A. R. H. , Ludbrook B. M. , Downes J. E. , Ruck B. J. , Durbin S. M.
Published: February 2010

We report structural and electronic properties of epitaxial hafnium nitride films grown on MgO by plasma-assisted pulsed laser deposition. The electronic structure measured using soft x-ray absorption and emission spectroscopy is in excellent agreement with the results of a band structure calculation. We show that by varying the growth conditions we can extend the films’ reflectance further toward the UV, and we relate this observation to the electronic structure.
Indigenous-Inclusive Citizenship: The City and Social Housing in Canada, New Zealand, and Australia
Authors: Walker Ryan , Barcham Manuhuia
Published: February 2010

Indigenous peoples in Canada, New Zealand, and Australia are highly urbanised. In spite of this, urban Indigenous communities have a difficult time giving effect to self-determining autonomy in comparison with their rural, remote, and reserve counterpart communities. The place of authentic Indigeneity in the public perception has remained outside of urban areas. All three countries have had social housing initiatives that aim to even out life-chances among citizens. How Indigeneity features in the housing sector varies from country to country. Through an examination of social housing developments from the 1930s to the present, we develop knowledge of how the place of authentic Indigeneity has changed over time and has been linked to the creation of Indigenous-inclusive citizenship in the city. While the Canadian experience continues to pair self-government with common social housing goals, New Zealand never really linked self-government with common social citizenship in the housing sector; Australia did for a time, but it is regressing quickly.
‘Wee Women No More’: Female Partners of Republican Political Prisoners in Belfast
Authors: Shirlow Peter , Dowler Lorraine
Published: February 2010

Studies of the female partners of politically motivated prisoners have generally studied women via a caring paradigm. Less well observed are those women who privately transgressed and challenged masculine-centred renditions or political imprisonment. This lacuna in the research dedicated to such women has been constructed around stereotypical depictions of them as a barely visible support network. We argue that the relatively indiscernible appearance of women who challenged such typecasting is attached to a persistent process of gender blindness within which women remain peripheral to wider narratives of collectivity and ideological presentation. We chart how some women actively involved themselves in creating their own identity as active agents, especially when the effects of conflict entered the private sphere.
Measurements of nanoparticle number concentrations and size distributions in contrasting aquatic environments using nanoparticle tracking analysis
Authors: Gallego-Urrea Julián A. , Tuoriniemi Jani , Pallander Tobias , Hassellöv Martin
Published: February 2010

Environmental context. Manufactured and unintentionally produced nanoparticles have been of environmental concern owing to potential harm to humans and ecosystems, but very little is known of the actual concentrations of these owing to limitations of available methods. In order to understand both the potential adverse effects and the underlying natural processes, improved measurement techniques are needed. Here, we explore the feasibility of a novel minimum perturbation method that relates the diffusive movement of nanoparticles in a light field to their size distributions.
Abstract. A feasibility study of nanoparticle tracking analysis (NTA) for aquatic environmental samples is presented here. The method has certain virtues such as minimum perturbation of the samples, high sensitivity in terms of particle concentration, and provision of number-based size distributions for aquatic samples. NTA gave linear calibration curves in terms of number concentration and accurately reproduced size measurements of certified reference material nanoparticles. However, the accuracy of the size distributions obtained with this method exhibited a high dependence on set-up parameters and the concentrations were shown to be strongly correlated with the refractive index of the material under examination. Different detection cameras and different data acquisition modes were compared and evaluated. Also, the effect of filtration of the samples was assessed. The size distributions for the contrasting environmental samples were fairly reasonable compared with other studies but an underestimation of small sizes was observed, which can be explained by a material-dependent lower detection limit in terms of size. The number concentrations obtained for the natural nanoparticles ranged from 0.5 to 20 × 108 particles mL–1 and correlated well with conventional turbidity measurements.
Physico-chemical behaviour and algal toxicity of nanoparticulate CeO2 in freshwater
Authors: Rogers Nicola J. , Franklin Natasha M. , Apte Simon C. , Batley Graeme E. , Angel Brad M. , Lead Jamie R. , Baalousha Mohammed
Published: February 2010

Environmental context. It cannot be assumed that nanomaterials entering aquatic environments will have the same impacts on aquatic biota as their macroscopic particle equivalents. If their toxicities are different, this will have implications for the way in which nanomaterial usage is regulated. Algae, at the bottom of the food chain, are likely to be a sensitive indicator of toxic effects. Understanding the physical and chemical factors controlling nanoparticle toxicity to algae will assist in evaluating their ecological risk.
Abstract. In assessing the risks posed by nanomaterials in the environment, the overriding research challenges are to determine if nanomaterials are more toxic than the bulk forms of the same material, and the extent to which toxicity is governed by particle size and reactivity. In this study, the toxicity of nanoparticulate CeO2 (nominally 10–20 nm) to the freshwater alga Pseudokirchneriella subcapitata was compared to the same material at the micron size (nominally <5 μm). Growth inhibition experiments revealed inhibitory concentration values, giving 50% reduction in algal growth rate after 72 h (IC50), of 10.3 ± 1.7 and 66 ± 22 mg L–1 for the nanoparticles and bulk materials respectively. Cells exposed to CeO2 particles were permeable to the DNA-binding dye SYTOX® Green in a concentration-dependent manner indicating damage to the cell membrane. Screening assays to assess the oxidative activity of the particles showed that the light illumination conditions used during standard algal bioassays are sufficient to stimulate photocatalytic activity of CeO2 particles, causing the generation of hydroxyl radicals and peroxidation of a model plant fatty acid. No oxidative activity or lipid peroxidation was observed in the dark. These findings indicate that inhibitory mode of action of CeO2 to P. subcapitata is mediated by a cell-particle interaction causing membrane damage. The effect is most likely photochemically induced and is enhanced for the nanoparticulate form of the CeO2.
Anchorage of VEGF to the extracellular matrix conveys differential signaling responses to endothelial cells
Authors: Chen Tom T. , Luque Alfonso , Lee Sunyoung , Anderson Sean M. , Segura Tatiana , Iruela-Arispe M. Luisa
Published: February 2010

VEGF can be secreted in multiple isoforms with variable affinity for extracellular proteins and different abilities to induce vascular morphogenesis, but the molecular mechanisms behind these effects remain unclear. Here, we show molecular distinctions between signaling initiated from soluble versus matrix-bound VEGF, which mediates a sustained level of VEGFR2 internalization and clustering. Exposure of endothelial cells to matrix-bound VEGF elicits prolonged activation of VEGFR2 with differential phosphorylation of Y1214, and extended activation kinetics of p38. These events require association of VEGFR2 with β1 integrins. Matrix-bound VEGF also promotes reciprocal responses on β1 integrin by inducing its association with focal adhesions; a response that is absent upon exposure to soluble VEGF. Inactivation of β1 integrin blocks the prolonged phosphorylation of Y1214 and consequent activation of p38. Combined, these results indicate that when in the context of extracellular matrix, activation of VEGFR2 is distinct from that of soluble VEGF in terms of recruitment of receptor partners, phosphorylation kinetics, and activation of downstream effectors.
Notch ligand activity is modulated by glycosphingolipid membrane composition in Drosophila melanogaster
Authors: Hamel Sophie , Fantini Jacques , Schweisguth François
Published: February 2010

Endocytosis of the transmembrane ligands Delta (Dl) and Serrate (Ser) is required for the proper activation of Notch receptors. The E3 ubiquitin ligases Mindbomb1 (Mib1) and Neuralized (Neur) regulate the ubiquitination of Dl and Ser and thereby promote both ligand endocytosis and Notch receptor activation. In this study, we identify the α1,4-N-acetylgalactosaminyltransferase-1 (α4GT1) gene as a gain of function suppressor of Mib1 inhibition. Expression of α4GT1 suppressed the signaling and endocytosis defects of Dl and Ser resulting from the inhibition of mib1 and/or neur activity. Genetic and biochemical evidence indicate that α4GT1 plays a regulatory but nonessential function in Notch signaling via the synthesis of a specific glycosphingolipid (GSL), N5, produced by α4GT1. Furthermore, we show that the extracellular domain of Ser interacts with GSLs in vitro via a conserved GSL-binding motif, raising the possibility that direct GSL–protein interactions modulate the endocytosis of Notch ligands. Together, our data indicate that specific GSLs modulate the signaling activity of Notch ligands.
Metabolic control of G1–S transition: cyclin E degradation by p53-induced activation of the ubiquitin–proteasome system
Authors: Mandal Sudip , Freije William A. , Guptan Preeta , Banerjee Utpal
Published: February 2010

Cell cycle progression is precisely regulated by diverse extrinsic and intrinsic cellular factors. Previous genetic analysis in Drosophila melanogaster has shown that disruption of the mitochondrial electron transport chain activates a G1–S checkpoint as a result of a control of cyclin E by p53. This regulation does not involve activation of the p27 homologue dacapo in flies. We demonstrate that regulation of cyclin E is not at the level of transcription or translation. Rather, attenuated mitochondrial activity leads to transcriptional upregulation of the F-box protein archipelago, the Fbxw7 homologue in flies. We establish that archipelago and the proteasomal machinery contribute to degradation of cyclin E in response to mitochondrial dysfunction. Our work provides in vivo genetic evidence for p53-mediated integration of metabolic stress signals, which modulate the activity of the ubiquitin–proteasome system to degrade cyclin E protein and thereby impose cell cycle arrest.
Needlestick Injury Rates According to Different Types of Safety-Engineered Devices: Results of a French Multicenter Study
Authors: Tosini William , Ciotti Céline , Goyer Floriane , Lolom Isabelle , L'Hériteau François , Abiteboul Dominique , Pellissier Gerard , Bouvet Elisabeth
Published: February 2010

Objectives.

To evaluate the incidence of needlestick injuries (NSIs) among different models of safety-engineered devices (SEDs) (automatic, semiautomatic, and manually activated safety) in healthcare settings.

Design.

This multicenter survey, conducted from January 2005 through December 2006, examined all prospectively documented SED-related NSIs reported by healthcare workers to their occupational medicine departments. Participating hospitals were asked retrospectively to report the types, brands, and number of SEDs purchased, in order to estimate SED-specific rates of NSI.

Setting.

Sixty-one hospitals in France.

Results.

More than 22 million SEDs were purchased during the study period, and a total of 453 SED-related NSIs were documented. The mean overall frequency of NSIs was 2.05 injuries per 100,000 SEDs purchased. Device-specific NSI rates were compared using Poisson approximation. The 95% confidence interval was used to define statistical significance. Passive (fully automatic) devices were associated with the lowest NSI incidence rate. Among active devices, those with a semiautomatic safety feature were significantly more effective than those with a manually activated toppling shield, which in turn were significantly more effective than those with a manually activated sliding shield (P < .001, x2 test). The same gradient of SED efficacy was observed when the type of healthcare procedure was taken into account.

Conclusions.

Passive SEDs are most effective for NSI prevention. Further studies are needed to determine whether their higher cost may be offset by savings related to fewer NSIs and to a reduced need for user training.
Subsets of migrating intestinal dendritic cells
Authors: Milling Simon , Yrlid Ulf , Cerovic Vuk , MacPherson Gordon
Published: February 2010

Dendritic cells (DCs) in the intestine are heterogeneous. Phenotypically different populations of conventional DCs have been identified in the intestinal lamina propria, Peyer’s patches, and in the draining mesenteric lymph nodes, to which these DCs constitutively migrate. Markers used to identify these populations include major histocompatibility complex class II, CD11c, CD8α, CD11b, and CD103. Extensive studies in rats, summarized here, which involved collection of migrating DCs by thoracic duct cannulation after mesenteric lymphadenectomy, have clearly demonstrated that the subsets of migrating intestinal lymph DCs have different functional properties. The subsets might play different roles in the induction of oral tolerance and in driving systemic immune responses after vaccination or intestinal stimulation with Toll‐like receptor ligands. The use of these surgical techniques allows investigation of the functions of purified subsets of migrating DCs. However, in the rat, these studies are limited by the range of available reagents and are difficult to compare with data from other species in this fast‐moving field. Recent refinements have enabled the collection of migrating intestinal DCs from mice; our initial results are described here. We believe that these studies will generate exciting data and have the potential to resolve important questions about the functions of migrating intestinal DC subsets.
The CD8+ dendritic cell subset
Authors: Shortman Ken , Heath William R.
Published: February 2010

Summary:  Mouse lymphoid tissues contain a subset of dendritic cells (DCs) expressing CD8α together with a pattern of other surface molecules that distinguishes them from other DCs. These molecules include particular Toll‐like receptor and C‐type lectin pattern recognition receptors. A similar DC subset, although lacking CD8 expression, exists in humans. The mouse CD8+ DCs are non‐migrating resident DCs derived from a precursor, distinct from monocytes, that continuously seeds the lymphoid organs from bone marrow. They differ in several key functions from their CD8− DC neighbors. They efficiently cross‐present exogenous cell‐bound and soluble antigens on major histocompatibility complex class I. On activation, they are major producers of interleukin‐12 and stimulate inflammatory responses. In steady state, they have immune regulatory properties and help maintain tolerance to self‐tissues. During infection with intracellular pathogens, they become major presenters of pathogen antigens, promoting CD8+ T‐cell responses to the invading pathogens. Targeting vaccine antigens to the CD8+ DCs has proved an effective way to induce cytotoxic T lymphocytes and antibody responses.
Regulation of dendritic cell differentiation and function by Notch and Wnt pathways
Authors: Cheng Pingyan , Zhou Jie , Gabrilovich Dmitry
Published: February 2010

Summary:  The process of dendritic cell differentiation is governed by a tightly controlled signaling network regulated by cytokines and direct interaction between progenitor cells and bone marrow stroma. Notch signaling represents one of the major pathways activated during direct interaction between hematopoietic progenitor cells and bone marrow stroma. Wnt pathway is activated by soluble proteins produced by bone marrow stroma. Until recently, the role of Notch and Wnt signaling in the development of myeloid cells and dendritic cells in particular remained unclear. In this review, we discuss recent exciting findings that shed light on the critical role of Notch and Wnt pathways, their interaction in differentiation and function of dendritic cells, and their impact on immune responses.
Development and functional specialization of CD103+ dendritic cells
Authors: Del Rio Maria‐Luisa , Bernhardt Günter , Rodriguez‐Barbosa Jose‐Ignacio , Förster Reinhold
Published: February 2010

Summary:  CD103 (αE) integrin expression distinguishes a population of dendritic cells (DCs) that can be found in many if not all lymphoid and non‐lymphoid organs. CD103+ DCs display distinct functional activities. Migratory CD103+ DCs derived from skin, lung, and intestine efficiently present exogenous antigens in their corresponding draining lymph nodes to specific CD8+ T cells through a mechanism known as cross‐presentation. On the T cells they prime, intestinal CD103+ DCs can drive the induction of the chemokine receptor CCR9 and α4β7 integrin, both known as gut‐homing receptors. CD103+ DCs also contribute to control inflammatory responses and intestinal homeostasis by fostering the conversion of naive T cells into induced Foxp3+ regulatory T cells, a mechanism that relies on transforming growth factor‐β and retinoic acid signaling. This review discusses recent findings that identify murine CD103+ DCs as important regulators of the immune response.
Origin and development of dendritic cells
Authors: Liu Kang , Nussenzweig Michel C.
Published: February 2010

Summary:  Dendritic cells (DCs) are specialized antigen‐presenting cells and essential mediators of immunity and tolerance. This group of cells is heterogeneous in terms of cell‐surface markers, anatomic location, and function. Here, we review the development and function of DCs found in lymphoid and non‐lymphoid tissues in the steady state. DC and monocyte lineages originate from a common progenitor, the monocyte and dendritic cell progenitor (MDP). The two cell types diverge when MDPs give rise to monocytes and committed DC progenitors (CDPs) in the bone marrow. CDPs give rise to pre‐DCs, which migrate from the bone marrow to lymphoid and non‐lymphoid tissues to produce the two major subpopulations of lymphoid tissue DCs and non‐lymphoid tissue CD103+ DCs. Within tissues and during development, DC division and homeostasis are regulated by the hormone Flt3L.
Langerhans cell histiocytosis: fascinating dynamics of the dendritic cell–macrophage lineage
Authors: Maarten Egeler R. , Van Halteren Astrid G. S. , Hogendoorn Pancras C. W. , Laman Jon D. , Leenen Pieter J. M.
Published: February 2010

Summary:  In its rare occurrence, Langerhans cell histiocytosis (LCH) is a dangerous but intriguing deviation of mononuclear phagocytes, especially dendritic cells (DCs). Clinically, the disease ranges from self‐resolving or well manageable to severe and even fatal. LCH lesions in skin, bone, and other sites contain high numbers of cells with phenotypic features resembling LCs admixed with macrophages, T cells, eosinophils, and multinucleated giant cells. Here we review current progress in the LCH field based on two central questions: (i) are LCH cells intrinsically aberrant, and (ii) how does the lesion drive pathogenesis? We argue that LCH cells may originate from different sources, including epidermal LCs, tissue Langerin+ DCs, or mononuclear phagocyte precursors. Current and prospective in vitro and in vivo models are discussed. Finally, we discuss recent insights into plasticity of T‐helper cell subsets in light of the lesion microenvironment. LCH continues to provide urgent clinical questions thereby inspiring innovative DC lineage research.
Harnessing human dendritic cell subsets for medicine
Authors: Ueno Hideki , Schmitt Nathalie , Klechevsky Eynav , Pedroza‐Gonzalez Alexander , Matsui Toshimichi , Zurawski Gerard , Oh SangKon , Fay Joseph , Pascual Virginia , Banchereau Jacques , Palucka Karolina
Published: February 2010

Summary:  Immunity results from a complex interplay between the antigen‐non‐specific innate immune system and the antigen‐specific adaptive immune system. The cells and molecules of the innate system employ non‐clonal recognition receptors including lectins, Toll‐like receptors, NOD‐like receptors, and helicases. B and T lymphocytes of the adaptive immune system employ clonal receptors recognizing antigens or their derived peptides in a highly specific manner. An essential link between innate and adaptive immunity is provided by dendritic cells (DCs). DCs can induce such contrasting states as immunity and tolerance. The recent years have brought a wealth of information on the biology of DCs revealing the complexity of this cell system. Indeed, DC plasticity and subsets are prominent determinants of the type and quality of elicited immune responses. In this article, we summarize our recent studies aimed at a better understanding of the DC system to unravel the pathophysiology of human diseases and design novel human vaccines.
Langerhans cells and more: langerin‐expressing dendritic cell subsets in the skin
Authors: Romani Nikolaus , Clausen Björn E. , Stoitzner Patrizia
Published: February 2010

Summary:  Langerhans cells (LCs) are antigen‐presenting dendritic cells (DCs) that reside in epithelia. The best studied example is the LC of the epidermis. By electron microscopy, their identifying feature is the unique rod‐ or tennis racket‐shaped Birbeck granule. The phenotypic hallmark is their expression of the C‐type lectin receptor langerin/CD207. Langerin, however, is also expressed on a recently discovered population of DC in the dermis and other tissues of the body. These ‘dermal langerin+ dendritic cells’ are unrelated to LCs. The complex field of langerin‐negative dermal DCs is not dealt with here. In this article, we briefly review the history, ontogeny, and homeostasis of LCs. More emphasis is laid on the discussion of functional properties in vivo. Novel models using genetically engineered mice are contributing tremendously to our understanding of the role of LCs in eliciting adaptive immune responses against pathogens or tumors and in inducing and maintaining tolerance against self antigens and innocuous substances in vivo. Also, innate effector functions are increasingly being recognized. Current activities in this area are reviewed, and possibilities for future exploitation of LC in medicine, e.g. for the improvement of vaccines, are contemplated.
DC subsets in positive and negative regulation of immunity
Authors: Coquerelle Caroline , Moser Muriel
Published: February 2010

Summary:  Since their discovery in 1973, dendritic cells (DCs) have gained strong interest from immunologists because of their unique capacity to sensitize naive T cells. There is now strong evidence that cells of the dendritic family not only control immunity but also regulate responses to self and non‐self, thereby avoiding immunopathology. These two complementary functions are critical to ensure the integrity of the organism in an environment full of antigens. How DCs display these opposite functions is still intriguing. Here, we review the role of DC subsets in the regulation of T‐helper responses in vivo.
Attenuated Bordetella pertussis vaccine strain BPZE1 modulates allergen‐induced immunity and prevents allergic pulmonary pathology in a murine model
Authors: Kavanagh H. , Noone C. , Cahill E. , English K. , Locht C. , Mahon B. P.
Published: February 2010

Background
Virulent Bordetella pertussis, the causative agent of whooping cough, exacerbates allergic airway inflammation in a murine model of ovalbumin (OVA) sensitization. A live genetically attenuated B. pertussis mucosal vaccine, BPZE1, has been developed that evokes full protection against virulent challenge in mice but the effect of this attenuated strain on the development of allergic responses is unknown.

Objective
To assess the influence of attenuated B. pertussis BPZE1 on OVA priming in a murine model of allergic airway inflammation.

Methods
Mice were challenged with virulent or attenuated strains of B. pertussis, and sensitized to allergen (OVA) at the peak of bacterial carriage. Subsequently, airway pathology, local inflammation and OVA‐specific immunity were examined.

Results
In contrast to virulent B. pertussis, live BPZE1 did not exacerbate but reduced the airway pathology associated with allergen sensitization. BPZE1 immunization before allergen sensitization did not have an adjuvant effect on allergen specific IgE but resulted in a statistically significant decrease in airway inflammation in tissue and bronchoalveolar lavage fluid. BPZE1 significantly reduced the levels of OVA‐driven IL‐4, IL‐5 and IL‐13 but induced a significant increase in IFN‐γ in response to OVA re‐stimulation.

Conclusions
These data demonstrate that, unlike virulent strains, the candidate attenuated B. pertussis vaccine BPZE1 does not exacerbate allergen‐driven airway pathology. BPZE1 may represent an attractive T‐helper type 1 promoting vaccine candidate for eradication of whooping cough that is unlikely to promote atopic disease.
Sublingual grass pollen immunotherapy is associated with increases in sublingual Foxp3‐expressing cells and elevated allergen‐specific immunoglobulin G4, immunoglobulin A and serum inhibitory activity for immunoglobulin E‐facilitated allergen binding to B cells
Authors: Scadding G. W. , Shamji M. H. , Jacobson M. R. , Lee D. I. , Wilson D. , Lima M. T. , Pitkin L. , Pilette C. , Nouri‐Aria K. , Durham S. R.
Published: February 2010

Background
The mechanisms of sublingual immunotherapy (SLIT) are less well understood than those of subcutaneous immunotherapy (SCIT).

Objectives
To determine the effects of grass‐pollen SLIT on oral mucosal immune cells, local regulatory cytokines, serum allergen‐specific antibody subclasses and B cell IgE‐facilitated allergen binding (IgE‐FAB).

Methods
Biopsies from the sublingual mucosa of up to 14 SLIT‐treated atopics, nine placebo‐treated atopics and eight normal controls were examined for myeloid dendritic cells (mDCs) (CD1c), plasmacytoid dendritic cells (CD303), mast cells (AA1), T cells (CD3) and Foxp3 using immunofluorescence microscopy. IL‐10 and TGF‐β mRNA expression were identified by in situ hybridization. Allergen‐specific IgG and IgA subclasses and serum inhibitory activity for binding of allergen‐IgE complexes to B cells (IgE‐FAB) were measured before, during and on the completion of SLIT.

Results
Foxp3+ cells were increased in the oral epithelium of SLIT‐ vs. placebo‐treated atopics (P=0.04). Greater numbers of subepithelial mDCs were present in placebo‐treated, but not in SLIT‐treated, atopics compared with normal controls (P=0.05). There were fewer subepithelial mast cells and greater epithelial T cells in SLIT‐ compared with placebo‐treated atopics (P=0.1 for both). IgG1 and IgG4 were increased following SLIT (P<0.001). Peak seasonal IgA1 and IgA2 were increased during SLIT (P<0.05). There was a time‐dependent increase in serum inhibitory activity for IgE‐FAB in SLIT‐treated atopics.

Conclusions
SLIT with grass pollen extract is associated with increased Foxp3+ cells in the sublingual epithelium and systemic humoral changes as observed previously for SCIT.

Cite this as: G. W. Scadding, M. H. Shamji, M. R. Jacobson, D. I. Lee, D. Wilson, M. T. Lima, L. Pitkin, C. Pilette, K. Nouri‐Aria and S. R. Durham, Clinical & Experimental Allergy, 2010 (40) 598–606.
Increase in dopa-positive melanocytes in the mouse intestine in response to ultraviolet B rays via the eyes
Authors: Hiramoto K.
Published: February 2010

Background. Irradiation by ultraviolet (UV) initiates pigmentation of skin; however, it is not known whether changes in intestinal pigmentation are also induced by UVB irradiation of the eye.

Aim. To examine the influence of UVB irradiation of the eye or ear on the pigmentation of mouse epidermis and intestine.

Methods. DBA/2 male mice were locally exposed to UVB (280–320 nm) using a 20SE sunlamp directed at the eye or ear. The irradiation was given over 3 days, at a dosage of 2.5 kJ/m2 per day. Five days after irradiation, samples were taken from the skin and intestine. Melanocytes in both epidermis and intestine were stained for dopa and expression of melanocortin-1 receptor (MC1R). Levels of plasma α-melanocyte-stimulating hormone (α-MSH) were measured using ELISA.

Results. Ultraviolet B irradiation of either the eye or ear in increased the number of dopa-positive melanocytes in the skin and the intestine (jejunum and colon). Irradiation of the eye caused a much greater increase in dopa than did irradiation of the ear. Both eye and ear irradiation increased blood α-MSH level to a similar extent, but only irradiation to the eye increased MC1R expression in the intestine.

Conclusions. These results suggest that the UVB-induced pigmentation in the epidermis and the intestine is related to increased levels of α-MSH and MC1R.
Rearing environment affects development of the immune system in neonates
Authors: Inman C F , Haverson K , Konstantinov S R , Jones P H , Harris C , Smidt H , Miller B , Bailey M , Stokes C
Published: February 2010

Early-life exposure to appropriate microbial flora drives expansion and development of an efficient immune system. Aberrant development results in increased likelihood of allergic disease or increased susceptibility to infection. Thus, factors affecting microbial colonization may also affect the direction of immune responses in later life. There is a need for a manipulable animal model of environmental influences on the development of microbiota and the immune system during early life. We assessed the effects of rearing under low- (farm, sow) and high-hygiene (isolator, milk formula) conditions on intestinal microbiota and immune development in neonatal piglets, because they can be removed from the mother in the first 24 h for rearing under controlled conditions and, due to placental structure, neither antibody nor antigen is transferred in utero. Microbiota in both groups was similar between 2 and 5 days. However, by 12–28 days, piglets reared on the mother had more diverse flora than siblings reared in isolators. Dendritic cells accumulated in the intestinal mucosa in both groups, but more rapidly in isolator piglets. Importantly, the minority of 2–5-day-old farm piglets whose microbiota resembled that of an older (12–28-day-old) pig also accumulated dendritic cells earlier than the other farm-reared piglets. Consistent with dendritic cell control of T cell function, the effects on T cells occurred at later time-points, and mucosal T cells from high-hygiene, isolator pigs made less interleukin (IL)-4 while systemic T cells made more IL-2. Neonatal piglets may be a valuable model for studies of the effects of interaction between microbiota and immune development on allergy.
Expression of p16INK4A in gastrointestinal stromal tumours (GISTs): two different forms exist that independently correlate with poor prognosis
Authors: Haller Florian , Agaimy Abbas , Cameron Silke , Beyer Manori , Gunawan Bastian , Happel Nicole , Langer Claus , Ramadori Giuliano , Von Heydebreck Anja , Füzesi László
Published: February 2010

Haller F, Agaimy A, Cameron S, Beyer M, Gunawan B, Happel N, Langer C, Ramadori G, von Heydebreck A & Füzesi L (2010) Histopathology56, 305–318

Expression of p16

INK4A

in gastrointestinal stromal tumours (GISTs): two different forms exist that independently correlate with poor prognosis

Aims:  To determine the prognostic impact of p16INK4A expression in gastrointestinal stromal tumours (GISTs), which is currently being questioned, with both loss and overexpression said to be correlated with poor prognosis.

Methods and results:  Two different forms of p16INK4A were identified, presenting with predominantly nuclear and cytoplasmic expression pattern, respectively. The immunohistochemical expression of the two forms and their correlation with E2F1 and prognosis were analysed in a series of 120 GISTs with clinical follow‐up. Low nuclear p16INK4A expression correlated with E2F1 up‐regulation, higher mitotic counts, and tumour progression. The prognostic value of nuclear p16INK4A expression was only marginally significant (P = 0.05). Strong expression of the cytoplasmic p16INK4A form was significantly associated with shorter disease‐free survival (P = 2 × 10−5). The prognostic impact of strong expression of the cytoplasmic p16INK4A form was independent of anatomical localization, tumour size and mitotic counts, and significant even among the cohort of tumours with high malignant potential.

Conclusions:  Low expression of the nuclear p16INK4A form and strong expression of the cytoplasmic p16INK4A form both represent two independent parameters each associated with tumour progression in GISTs. Low nuclear p16INK4A expression enables E2F1 up‐regulation and consecutive accelerated cell proliferation. In contrast, strong cytoplasmic p16INK4A expression probably reflects a negative feedback loop as a result of (as yet unknown) oncogenic events.
A UK NEQAS ICC and ISH multicentre study using the Kreatech Poseidon HER2 FISH probe: intersite variation can be rigorously controlled using FISH
Authors: Bartlett John M S , Campbell Fiona M , Ibrahim Merdol , Thomas Jeremy , Wencyk Pete , Ellis Ian , Kay Elaine , Connolly Yvonne , O’Grady Anthony , Barnett Sarah , Starczynski Jane , Cunningham Paul , Miller Keith
Published: February 2010

Bartlett J M S, Campbell F M, Ibrahim M, Thomas J, Wencyk P, Ellis I, Kay E, Connolly Y, O’Grady A, Barnett S, Starczynski J, Cunningham P & Miller K (2010) Histopathology56, 297–304

A UK NEQAS ICC and ISH multicentre study using the Kreatech Poseidon HER2 FISH probe: intersite variation can be rigorously controlled using FISH

Aim:  To assess a new HER2 fluorescence in situ hybridization (FISH) test and report on multicentre intrasite and intersite variation.

Methods and results:  HER2 results were scored from 45 breast cancers in eight laboratories using the Kreatech Poseidon™HER2 FISH probe (Kreatech Diagnostics, Amsterdam, the Netherlands). Overall, 80.9% of cores were successfully analysed. Mean intrasite variation for HER2 ratio assessment was low (4.74%). Intersite variation in ratio was in line with previous reports (11.9 ± 0.8%) for both reference and non‐reference laboratories; only one laboratory displayed significantly higher intersite variation (P = 0.009) than the remaining seven laboratories. The overall incidence of misclassification of cores was <1.3%, demonstrating an excellent level of concordance (>98.7%) across all eight laboratories, irrespective of whether they were ‘reference’ or ‘routine diagnostic’ laboratories.

Conclusions:  The Kreatech Poseidon™HER2 FISH test is robust and reproducible. Highly quantitatively reproducible FISH results were obtained from eight ‘diagnostic’ and ‘reference’ laboratories; however, continued quality assessments are essential to good performance.
Cortisone replacement therapy in endocrine disorders – quality of self‐care
Authors: Harsch Igor A. , Schuller Andrea , Hahn Eckhart G. , Hensen Johannes
Published: February 2010

Objective  Some endocrine disorders make cortisone replacement therapy (CRT) mandatory. Patients need to be well informed about the therapy and to be able to adapt the dose in case of stress, trauma or surgery. It is unknown where the patients mainly get their information from and what their preferences in learning about the disease are, as well as what their ideas are on how to improve the knowledge transfer.

Study design  We used an anonymized questionnaire to evaluate these objectives as well as the patients' present state of knowledge.

Patients and Methods  A total of 338 patients with Addison's disease, hypopituitarism or adrenogenital syndrome (mean age 39.8 ± 21.1 years, mean duration of disease 11.4 ± 10.8 years) took part in the study.

Results  Spoken information by doctors is the main source of information for the patients (89%). Apart from counselling by physicians, journals of self‐help groups (66%), brochures/guidebooks (60%) and the Internet (45%) are important sources of information. Asked for suggestions for further improvement of knowledge transfer, information available on paper is still the first choice (65%). 51.9% of the questions about CRT were answered correctly. 24% of the patients reported hospitalizations because of Addisonian crisis.

Conclusion  Information transfer by doctors is the main source of information for the patients. The low patient numbers make the development of structured education programmes unlikely. Given that only the half of the answers in the ‘knowledge’ section of the questionnaire were correct, the available media could contribute to the improvement of information transfer.
Major elective joint replacement surgery: socioeconomic variations in surgical risk, postoperative morbidity and length of stay
Authors: Hollowell Jennifer , Grocott Mike P. W. , Hardy Rebecca , Haddad Fares S. , Mythen Monty G. , Raine Rosalind
Published: February 2010

Background  Patient deprivation is associated with greater need for total hip and knee replacement surgery (THR/TKR) and a higher prevalence of risk factors for surgical complications. Our aim was to examine associations between deprivation and aspects of the inpatient episode for patients undergoing these procedures.

Methods  We analysed socioeconomic variations in preoperative surgical risk, postoperative morbidity and length of stay for 655 patients undergoing elective THR/TKR at a large metropolitan hospital. Surgical risk was assessed using the orthopaedic version of the POSSUM scoring system, postoperative morbidity was assessed using the postoperative morbidity survey, and socioeconomic status was measured using the Index of Multiple Deprivation. We adjusted for age, sex, surgical site and primary vs. revision surgery.

Results  We found only a modest, clinically insignificant socioeconomic gradient in preoperative surgical risk and no socioeconomic gradient in postoperative morbidity. There was a strong socioeconomic gradient in length of stay, but only for patients undergoing TKR. This was due to deprived patients being more likely to remain in hospital without morbidity following TKR.

Conclusions  Our findings suggest differential selection of healthier patients for surgery. Hospitals serving deprived communities may have excess, unfunded costs because of the increased length of stay of socioeconomically disadvantaged patients.
Prevalence and distribution of sensitization to foods in the European Community Respiratory Health Survey: a EuroPrevall analysis
Authors: Burney P. , Summers C. , Chinn S. , Hooper R. , Van Ree R. , Lidholm J.
Published: February 2010

To cite this article: Burney P, Summers C, Chinn S, Hooper R, van Ree R, Lidholm J. Prevalence and distribution of sensitization to foods in the European Community Respiratory Health Survey: a EuroPrevall analysis. Allergy 2010; 65: 1182–1188.

Background:  Reports of adverse reactions to foods are increasing, but there is limited information on the comparative prevalence of sensitization to food allergens using standardized methods.

Methods:  Sera from the ‘random sample’ of young adults seen during the second phase of the European Community Respiratory Health Survey were analysed for IgE against 24 foods using ImmunoCAP. Sera were tested on five food mixes, and subsequently on individual foods in each positive mix.

Results:  Sera from 4522 individuals living in 13 countries were tested for at least one food allergen mix. Prevalence of sensitization to any of the 24 food allergens ranged from 24.6% in Portland (USA) to 7.7% in Reykjavik (Iceland). With few exceptions, the relative prevalence of sensitization to different foods was similar in all countries. Sensitization rates to egg, fish and milk were each less than 1%, and the most common sensitizations are not represented in current commercial mixes. The prevalence of sensitization to foods was not related to that of sensitization to aeroallergens but was related to the geometric mean total IgE for the country.

Conclusions:  Sensitization to foods is common but highly variable. The relative prevalence of sensitization to different foods is more consistent than would be expected by chance, suggesting that quantity of consumption of specific foods does not determine prevalence. The aetiology of food sensitization is only partly similar to that for aeroallergens but is related to local levels of total IgE. This may provide an important clue to the origins of food sensitization.
POEMS syndrome with idiopathic portal hypertension: Autopsy case and review of the literature
Authors: Inoue Rie , Nakazawa Atsushi , Tsukada Nobuhiro , Katoh Yuko , Nagao Toshitaka , Nakanuma Yasuni , Mukai Kiyoshi
Published: February 2010

Polyneuropathy, organomegaly, endocrinopathy, M protein, and skin changes (POEMS) syndrome is a rare multi‐system disease. Reported herein is an autopsy case of POEMS syndrome in a subject who developed idiopathic portal hypertension (IPH). The patient was a 38‐year‐old woman who was initially admitted to the Saiseikai Central Hospital because of polyneuropathy and edema. Diagnosis of POEMS syndrome was established on additional symptoms (splenomegaly and papilloedema) and serum M‐protein. Corticosteroid was given for 10 years. The patient was admitted again at the age of 48 years because of gastrointestinal bleeding due to portal hypertension. The patient died of hepatoencephalopathy at 58 years of age. The liver at autopsy demonstrated dense portal fibrosis and obliteration of small portal vein branches, which are characteristic histological findings of IPH. Portal hypertension is a rare symptom in POEMS syndrome. Only three cases of IPH associated with POEMS syndrome (including the present one) have been reported so far. In the previous two reports, liver biopsy failed to determine the cause of portal hypertension. This is the first report on the occurrence of histological findings compatible with IPH in the liver. Although it is not confirmed whether IPH is related to POEMS syndrome, elevated serum cytokines such as vascular endothelial growth factor and coagulation abnormality could have contributed to the development of IPH in the present case.
Multiple endocrine neoplasia type 1‐associated cystic pancreatic endocrine neoplasia and multifocal cholesterol granulomas
Authors: Kimura Noriko , Komuro Kazuteru , Uchino Shinya , Yagihashi Soroku , Ishidate Takuzo , Ishizaka Masanori
Published: February 2010

A novel combination of tumors was found in a 68 year‐old female with Multiple Endocrine Neoplasia type‐1 (MEN 1) that included a cystic pancreatic endocrine neoplasm (CPEN), a pituitary adenoma, and multifocal cholesterol granulomas (MCGs) in the breast, pleura, and the extremities. The pancreatic tumor displayed a single central locule surrounded by a thin rim of neoplastic parenchyma. The tumor showed heterogeneity in the architecture that included glandular, trabecular and solid patterns. The tumor cells of the pancreas were immunohistochemically positive for both endocrine and pancreatic acinar markers including chromogranin A, synaptophysin, glucagon, lipase, and reg protein. Electron microscopy revealed that there were numerous smaller dense‐cored neurosecretory granules, larger zymogen‐like granules and microvilli on the apical side of the tumor cells. The pancreatic tumor was diagnosed as CPEN with acinar cell features. Analysis of the DNA extracted from the tissues revealed that there is a MEN1 germline mutation in exon 10 codon 527, and somatic mutation in exon 2 codon 32 in the pancreatic tumor, and one base pair deletion in exon 2 codon 79 in the pituitary adenoma. Here, we report the case and discuss possible pathogenesis of CPEN and MCGs in a patient with MEN 1.
Rock, paper and scissors? Traumatic paediatric cataract in Victoria 1992–2006
Authors: Staffieri Sandra E , Ruddle Jonathan B , Mackey David A
Published: February 2010

Abstract

Background:  To review visual acuity outcomes from paediatric traumatic cataract and examine the mechanisms by which they occur.

Methods:  A retrospective review of paediatric patients (aged less than 18 years) who underwent lens surgery following ocular trauma, between 1992 and 2006 at the Royal Children's Hospital and Royal Victorian Eye and Ear Hospital in Melbourne. Data collected included gender, mechanism of injury, wound type, age at injury, age at surgery, refractive rehabilitation, complications and visual acuity outcome.

Results:  A total of 74 patients (75% male) were identified over the 15‐year period, representing an incidence of 4.9 cases per year. The mean age at injury was 7.5 years. Sixty‐five cataracts (88%) followed a penetrating eye injury, whereas only nine patients (12%) developed cataract after known blunt trauma. Fourteen patients (19%) underwent lensectomy at the time of primary wound repair and 45 patients (61%) underwent primary intraocular lens (IOL) implantation. Visual acuity outcomes ranged from 6/5 to no perception of light. Twenty‐five patients (34%) achieved 6/12 or better in the injured eye, 23 patients (31%) achieved between 6/15 and 6/60, and 14 patients (19%) had visual acuity of less than 6/60. Twelve patients (16%) were lost to follow‐up.

Conclusion:  In a paediatric population, cataract formation as a result of trauma requiring lensectomy is not uncommon. Males are more likely to suffer from such injury. A variety of sharp and blunt objects are the primary mechanism by which the injury is sustained with variable visual outcomes.