bluuebunny/crossref_metadata_2025 huggingface dataset:
Conservation implications of genetic variation between spatially and temporally distinct colonies of the endangered damselfly Coenagrion mercuriale
Authors: Watts Phillip C. , Kemp Stephen J. , Saccheri Ilik J. , Thompson David J.
Published: September 2005

Abstract.  1. Good conservation management is underpinned by a thorough understanding of species' historical and contemporary dispersal capabilities along with the possible adaptive or neutral processes behind any spatio‐temporal genetic structuring. These issues are investigated with respect to the rare damselfly Coenagrion mercuriale (Charpentier) – the only odonate species currently listed in the U.K.'s Biodiversity Action Plan – in east Devon where its distribution has become fragmented.

2. The two east Devon C. mercuriale populations, only 3.5 km apart, have accumulated strong differences in frequencies of alleles at 14 microsatellite loci as a consequence of poor adult dispersal and drift. There is no contemporary migration between sites.

3. A genetic signature of population decline at both sites corresponds with known demographic reductions. Coenagrion mercuriale in east Devon are now significantly genetically less diverse than those from a population stronghold in the Itchen Valley.

4. Colonies would benefit from improved connectivity between areas and possibly by a transfer of individuals from other ecologically similar areas.

5. Because C. mercuriale has a semivoltine life cycle throughout the U.K., the possibility that alternate‐year cohorts are reproductively isolated is explored. Genetic differentiation among cohorts is an order of magnitude less than between sites, suggesting that some larvae delay their development into adults for a year and recruit to a different cohort.

6. To our knowledge, this is the first study to document migration and gene flow between alternate‐year cohorts in a species of odonate. From a conservation standpoint, the cohorts do not require separate management.
Resistance and tolerance to herbivory in Salix cordata are affected by different environmental factors
Authors: Macdonald Kevin P. , Bach Catherine E.
Published: September 2005

Abstract.  1. Effects of sand burial and nutrients on the ability of sand‐dune willow (Salix cordata) to tolerate or resist herbivory by the beetle Altica subplicata were evaluated in field experiments.

2. To assess tolerance, all combinations of sand burial (none, 50%), nutrients (presence, absence), and beetles (presence, absence) were applied to caged plants and growth responses to herbivory were measured. Sand burial increased plant growth rate, but decreased S. cordata's tolerance to herbivory. Although nutrients increased growth, tolerance to herbivory was unaffected.

3. To assess resistance, plants were exposed to all combinations of sand burial and nutrients, and then to natural beetle colonisation. The presence of nutrients, but not sand burial, significantly increased the percentage of plants with beetles, for both adults and larvae. This decreased resistance to beetles of plants grown with added nutrients occurred only in the absence of sand burial.

4. The performance and preference of beetles were examined in laboratory experiments. Larvae developed faster and had increased pupation success on plants with nutrients added. Beetles also showed a marginally significant feeding preference for leaves grown with added nutrients. Thus, S. cordata tolerance to herbivory was affected by sand burial, whereas resistance, preference, and performance were affected by nutrient level.
Facilitation of Extinction of Conditioned Fear by D-Cycloserine
Authors: Davis Michael , Myers Karyn M. , Ressler Kerry J. , Rothbaum Barbara O.
Published: September 2005

Excessive fear and anxiety are characteristic of disorders such as post-traumatic stress disorder (PTSD) and phobias and are believed to reflect abnormalities in neural systems governing the development and reduction of conditioned fear. Conditioned fear can be suppressed through a process known as extinction, in which repeated exposure to a feared stimulus in the absence of an aversive event leads to a gradual reduction in the fear response to that stimulus. Like conditioned fear learning, extinction is dependent on a particular protein (the N-methyl-D-aspartate or NMDA receptor) in a part of the brain called the amygdala. Blockade of this receptor blocks extinction and improving the activity of this receptor with a drug called D-cycloserine speeds up extinction in rats. Because exposure-based psychotherapy for fear disorders in humans resembles extinction in several respects, we investigated whether D-cycloserine might facilitate the loss of fear in human patients. Consistent with findings from the animal laboratory, patients receiving D-cycloserine benefited more from exposure-based psychotherapy than did placebo-treated controls. Although very preliminary, these data provide initial support for the use of cognitive enhancers in psychotherapy and demonstrate that preclinical studies in rodents can have direct benefits to humans.
Current Directions in Personnel Selection Research
Authors: Chan David
Published: September 2005

For many decades, the focus of personnel selection research was on developing selection tests that maximized prediction of job performance; the approach was typically lacking in theoretical bases. The past two decades saw significant shifts in research to a focus on the nature of constructs and their interrelationships, characterized by an approach that emphasizes theoretical understanding of the phenomena under investigation. This article provides an overview of how a construct-oriented approach underlies major current directions in scientific research on personnel selection. Emerging trends that are likely to constitute issues of enduring importance are discussed.
Allogeneic haematopoietic stem‐cell transplantation for relapsed and refractory aggressive histology non‐Hodgkin lymphoma*
Authors: Doocey Richard T. , Toze Cynthia L. , Connors Joseph M. , Nevill Thomas J. , Gascoyne Randy D. , Barnett Michael J. , Forrest Donna L. , Hogge Donna E. , Lavoie Julye C. , Nantel Stephen H. , Shepherd John D. , Sutherland Heather J. , Voss Nicholas J. , Smith Clayton A. , Song Kevin W.
Published: September 2005

Forty‐four patients with relapsed or refractory aggressive histology non‐Hodgkin lymphoma (NHL) (diffuse large B cell, n = 23; peripheral T cell, n = 5; transformed B cell, n = 16) proceeded to allogeneic stem cell transplant (allo‐SCT) between 1987 and 2003. Median age at transplant was 40 years (range 19–56 years). At the time of transplant, 35 were chemosensitive and nine were chemorefractory. Thirty‐three patients had matched sibling donors and 11 had unrelated donors. Forty‐two patients (95%) received radiation‐based conditioning regimens. Event‐free survival (EFS) and overall survival (OS) at 5 years was 43% [95% confidence interval (CI): 27–58%] and 48% (95% CI: 32–63%) respectively. Treatment‐related mortality was 25% at 1 year. Grade III–IV acute graft‐versus‐host disease (GVHD) was the only significant variable affecting OS and EFS, and had a negative impact. Chronic GVHD did not influence survival. Lymphoma relapse <12 months after initial therapy predicted for increased risk of relapse post‐transplant (P = 0·02). Patients with chemorefractory lymphoma were not at increased risk of relapse (P = 0·20) with four of nine patients remaining alive without disease 12–103 months post‐transplant. In conclusion, allo‐SCT for relapsed or refractory aggressive histology NHL results in long‐term EFS and OS of 40–50%. Patients with chemorefractory disease can have a durable remission post‐transplant.
Exercise capacity in patients with β‐thalassaemia intermedia
Authors: Agostoni Piergiuseppe , Cerino Mario , Palermo Pietro , Magini Alessandra , Bianchi Michele , Bussotti Maurizio , Fiorelli Gemino , Cappellini Maria D.
Published: September 2005

Thalassaemia intermedia patients can suffer fatigue and exercise capacity reduction, possibly because of anaemia, deconditioning and lack of exercise‐induced haemoconcentration. We studied 21 β‐thalassaemia intermedia patients, 10 splenectomised (group A) and 11 not splenectomised (group B). Patients were evaluated by cardiopulmonary exercise test with blood sampling for haemoglobin and plasma protein measurements at rest and peak. During exercise, an isolated increase of haemoglobin suggested spleen contraction while a parallel increase of haemoglobin and proteins suggested fluid filtration through capillary wall. Groups were homogeneous for age and gender. Peak oxygen consumption (VO2) was 22·5 ± 4·4 ml/min/kg (51 ± 14%) and 24·3 ± 7·0 (53 ± 12%) in groups A and B respectively [not significant (NS)]. At rest, haemoglobin was 8·8 g/dl in both groups. Exercise‐induced increment was 0·4 ± 0·2 and 1·0 ± 0·4 g/dl (P < 0·001) for haemoglobin and 4·0 ± 3·0 and 5·0 ± 4·0 g/l (NS) for proteins, in groups A and B respectively. Anaemia was the major cause of peak VO2 reduction (1097 ± 260 ml/min). However, anaemia did not explain the entire exercise capacity reduction, suggesting the presence of muscular deconditioning. Exercise capacity is reduced in β‐thalassaemia intermedia because of anaemia and muscular deconditioning. Spleen contraction does not significantly influence exercise capacity although exercise‐induced haemoconcentration was greater in patients with spleen.
Essential role of STAT3 in cytokine‐driven NF‐κB‐mediated serum amyloid A gene expression
Authors: Hagihara Keisuke , Nishikawa Teppei , Sugamata Yasuhiro , Song Jian , Isobe Tomoyasu , Taga Tetsuya , Yoshizaki Kazuyuki
Published: September 2005

Serum amyloid A (SAA) is a sensitive marker of acute‐phase responses and known as a precursor protein of amyloid fibril in amyloid A (AA) (secondary) amyloidosis. Since the serum SAA level is also closely related to activity of chronic inflammatory disease and coronary artery disease, it is important to clarify the exact induction mechanism of SAA from the clinical point of view. Here we provide evidence that STAT3 plays an essential role in cytokine‐driven SAA expression, although the human SAA gene shows no typical STAT3 response element (RE) in its promoters. STAT3 and nuclear factor κB (NF‐κB) p65 first form a complex following interleukin (IL)‐1 and IL‐6 (IL‐1+6) stimulation, after which STAT3 interacts with nonconsensus sequences at a 3′ site of the SAA gene promoter's NF‐κB RE. Moreover, co‐expression of p300 with STAT3 dramatically enhances the transcriptional activity of SAA. The formation of a complex with STAT3, NF‐κB p65, and p300 is thus essential for the synergistic induction of the SAA gene by IL‐1+6 stimulation. Our findings are expected to aid the understanding of the inflammatory status of AA amyloidosis to aid development of a therapeutic strategy for this disease by means of normalization of serum SAA levels.
Loss of phenotypic expression is related to tumour progression in early gastric differentiated adenocarcinoma
Authors: Nakamura T , Yao T , Kabashima A , Nishiyama K , Maehara Y , Tsuneyoshi M
Published: September 2005

Aims : To evaluate the relationship between phenotypic expression and tumour progression as represented by macroscopic features, submucosal invasion and lymph node metastasis in early differentiated gastric adenocarcinoma.

Methods : One hundred and fifty‐five cases of early gastric differentiated adenocarcinoma without any poorly differentiated components were studied. The mucosal and submucosal components of carcinomas and lymph node metastatic lesions were classified into four categories, gastric type (G‐type), incomplete intestinal type (I‐type), complete intestinal type (C‐type) and unclassified type (U‐type), based on the combination of the phenotypic expression of HGM (gastric foveolar epithelium), MUC6 (gastric pyloric glands), MUC2 (intestinal goblet cells) and CD10 (small intestinal brush border). In addition, a new classification representing a phenotypic shift from mucosa to submucosa or from primary lesion to lymph node metastasis was established with the categories of preserved group (P‐group), loss group (L‐group) and acquired group (A‐group).

Results : (1) In submucosal carcinoma, U‐type was more common in the submucosa (39%) than in the mucosa (9%). (2) U‐type was more common in the metastatic lesions (42%) than in the primary lesions (5%). (3) The submucosal component and lymph node metastatic lesions were classified as P‐group in 48% and 43% of cases, respectively, and as L‐group in 50% and 52% of cases, respectively. (4) Lymph node metastatic lesions comprising undifferentiated carcinoma were classified as L‐group in 100% of cases.

Conclusion : During the course of tumour progression, early differentiated adenocarcinoma at first tends to lose its phenotypic expression despite preserving its morphology, but subsequently morphological dedifferentiation occurs.
Therapeutic anti‐integrin (α4 and αL) monoclonal antibodies: two‐edged swords?
Authors: González‐Amaro Roberto , Mittelbrunn María , Sánchez‐Madrid Francisco
Published: September 2005

Anti‐α4 and anti‐αL integrin chain monoclonal antibodies have shown a clear‐cut beneficial effect in different animal models of autoimmune and inflammatory disorders as well as in human diseases, including multiple sclerosis, inflammatory bowel disease, and psoriasis. It has been widely assumed that this therapeutic effect is mainly consequence of the blockade of leucocyte adhesion to endothelium, inhibiting thus their extravasation and the inflammatory phenomenon. However, it is evident that both α4β1 (very late antigen‐4) and αLβ2 (leucocyte function‐associated antigen‐1) integrins have additional important roles in other immune phenomena, including the formation of the immune synapse and the differentiation of T helper 1 lymphocytes. Therefore, it is very feasible that the long‐term administration of blocking agents directed against these integrins to patients with inflammatory/autoimmune conditions may have undesirable or unexpected effects.
T cells are required for the peripheral phase of B‐cell maturation
Authors: Milićević Novica M. , Nohroudi Klaus , Milićević Živana , Hedrich Hans‐Juergen , Westermann Jürgen
Published: September 2005

B‐lymphocyte maturation is considered to be independent of the thymus. However, there is circumstantial evidence suggesting that it may be impaired in nude animals that lack the thymus. Our study shows that the proportion of immature B‐lymphocyte subsets (CD90high IgMhigh and CD90high IgMlow) was significantly increased, whereas that of mature B‐lymphocyte subsets (CD90– IgMlow and CD90– IgMhigh) was decreased in the blood and lymph nodes of nude rats. In addition, the expression of major histocompatibility complex class II, intercellular adhesion molecule‐1, CD44 and l‐selectin was significantly down‐regulated both on immature and mature B‐lymphocyte subsets. After implantation of thymic tissue under the kidney capsule of nude rats the block in B‐lymphocyte maturation was alleviated and the expression of surface molecules was normalized. Comparable effects were seen after the adoptive transfer of T lymphocytes. Thus, we show that in nude rats B cells do not mature properly because of the lack of T‐cell help and that T lymphocytes are required for the peripheral phase of B‐lymphocyte maturation, as well as for the appropriate expression of surface molecules. This should be considered when treating patients with T‐cell deficiencies.
Ligation of CD8α on human natural killer cells prevents activation‐induced apoptosis and enhances cytolytic activity
Authors: Addison Elena G. , North Janet , Bakhsh Ismail , Marden Chloe , Haq Sumaira , Al‐Sarraj Samia , Malayeri Reza , Wickremasinghe R. Gitendra , Davies Jeffrey K. , Lowdell Mark W.
Published: September 2005

It has been previously shown that the subset of human natural killer (NK) cells which express CD8 in a homodimeric α/α form are more cytotoxic than their CD8– counterparts but the mechanisms behind this differential cytolytic activity remained unknown. Target cell lysis by CD8– NK cells is associated with high levels of effector cell apoptosis, which is in contrast to the significantly lower levels found in the CD8α+ cells after lysis of the same targets. We report that cross‐linking of the CD8α chains on NK cells induces rapid rises in intracellular Ca2+ and increased expression of CD69 at the cell surface by initiating the influx of extracellular Ca2+ ions. We demonstrate that secretion of cytolytic enzymes initiates NK‐cell apoptosis from which CD8α+ NK cells are protected by an influx of exogenous calcium following ligation of CD8 on the NK‐cell surface. This ligation is through interaction with fellow NK cells in the cell conjugate and can occur when the target cells lack major histocompatibility complex (MHC) Class I expression. Protection from apoptosis is blocked by preincubation of the NK cells with anti‐MHC Class I antibody. Thus, in contrast to the CD8– subset, CD8α+ NK cells are capable of sequential lysis of multiple target cells.
The analysis of systemic tolerance elicited by antigen inoculation into the vitreous cavity: vitreous cavity‐associated immune deviation
Authors: Sonoda Koh‐Hei , Sakamoto Taiji , Qiao Hong , Hisatomi Toshio , Oshima Toru , Tsutsumi‐Miyahara Chikako , Exley Mark , Balk Steven P. , Taniguchi Masaru , Ishibashi Tatsuro
Published: September 2005

The immune privilege that exists in the eye is maintained by various mechanisms. One of the best studied is a form of systemic tolerance termed anterior chamber‐associated immune deviation (ACAID). We have investigated the mechanisms by which ocular inflammation associated with the vitreous cavity (VC) is reduced, by injecting either ovalbumin (OVA) or allogeneic splenocytes into the VCs of mice, and assessed the effect of this on delayed type hypersensitivity (DTH) responses. After antigen inoculation into the VC, antigen‐specific DTH responses were significantly impaired and we named this phenomenon ‘vitreous cavity‐associated immune deviation’ (VCAID). VCAID could also be induced by inoculating antigen‐pulsed macrophages into the VC. However, VCAID did not develop either in mice with inflamed eyes, whether as a result of experimental autoimmune uveitis or coadministration of interleukin (IL)‐6 in the VC, or in knockout mice deficient for natural killer T (NKT) cells. Finally, we found that so‐called ‘hyalocytes’ are the only cells present in the VCs of normal mice, uniformly distributed on the retinal surface. Interestingly, they express F4/80, suggesting that hyalocytes are candidate antigen‐presenting cells (APCs) responsible for mediating VCAID. As for the anterior chamber model, systemic tolerance can be induced in the VC in non‐inflamed eyes and in the presence of invariant NKT cells.
Evaluation of CD62L expression as a marker for vaccine‐elicited memory cytotoxic T lymphocytes
Authors: Jackson Shawn S. , Schmitz Jörn E. , Kuroda Marcelo J. , McKay Paul F. , Sumida Shawn M. , Martin Kristi L. , Yu Faye , Lifton Michelle A. , Gorgone Darci A. , Letvin Norman L.
Published: September 2005

The development of successful vaccination strategies for eliciting cytotoxic T lymphocytes (CTLs) will be facilitated by the definition of strategies for subdividing CTLs into functionally distinct subpopulations. We assessed whether surface expression of a number of cell‐surface proteins could be used to define functionally distinct subpopulations of memory CTLs in mice immunized with a recombinant vaccinia virus expressing human immunodeficiency virus (HIV)‐1 envelope (Env). We found changes in cell‐surface expression of CD11a, CD44, CD45RB, CD49d, CD54 and CD62L on Env‐specific CD8+ T cells that appeared to differentiate them from other CD8+ T cells within 1 week to 1 month following immunization. Further, we saw an up‐regulation of CD62L surface expression on Env‐specific CD8+ memory T cells several months after immunization. However, CD62L expression did not correlate with differences in the abilities of CTLs to proliferate or produce interferon gamma (IFN‐γ) and tumour necrosis factor alpha (TNF‐α) in vitro in response to Env peptide stimulation. Moreover, the expression of CD62L did not allow differentiation of CTLs into subpopulations with distinct expansion kinetics in vivo after adoptive transfer into naïve mice and subsequent boosting of these mice with a recombinant adenovirus expressing HIV‐1 Env. Therefore, the definition of memory CD8+ T‐cell subpopulations on the basis of CD62L expression in mice does not allow the delineation of functionally distinct CTL subpopulations.
Crossing complex boundaries: transnational online education in European trade unions
Authors: Walker S. , Creanor L.
Published: September 2005

AbstractCollaboration across boundaries in work and learning is increasingly a feature of networked organisation. We present a framework for analysing learning events as encounters across multiple boundaries of differing types, significance, role and severity. These boundaries may provide either/both obstacles to, and opportunities for, learning. Tutors and learners may negotiate these various boundaries with a variety of digital practices and artefacts. We apply this provisional framework of boundaries, artefacts and practices to the case of transnational trade union education, in which tutors and course participants negotiate a complex mix of boundaries. We identify ways in which practices and tools can have consequences for multiple boundaries and conclude that this approach provides a way to unpack some of the complexity of interactions in transnational learning situations and offers a framework to identify effective tools and practices.
Conferences as learning communities: some early lessons in using ‘back‐channel’ technologies at an academic conference – distributed intelligence or divided attention?
Authors: Jacobs N. , McFarlane A.
Published: September 2005

Abstract Most, if not all, researchers attend conferences as a part of their practice, and yet it is an under‐researched activity. Little attention has been paid either to developing a theoretically informed understanding of conference practice as knowledge building, or to assessing the extent to which conferences are successful. This paper addresses these issues in the context of a small empirical study of the introduction of mobile, interactive (‘back‐channel’) technologies into a conference setting. Science studies and learning theories literatures are used to develop an eight‐point statement describing the aims of an idealised conference. This is then used as a framework through which to make sense of what happened when ‘back‐channel’ technologies such as internet relay chat (IRC) and blogging were introduced into the 2004 Colston Symposium ‘The Evolution of Learning and Web Technologies: Survival of the Fittest?’. Focusing on sequential issues and the conference as a forum for knowledge building, the analysis shows that conference order is disrupted by the introduction of the back‐channel technologies. Nevertheless, other pressures on academic and professional practice (the governance agenda, calls for greater collaboration and a more consensual approach, and so on) suggest that the potential of the new technologies to help open up the black box of scientific and professional practice will be seen as increasingly important. If these tools are to be used effectively in the future, conferences will need to be supported by new skills and practices.
The prevalence of intellectual disability in Limburg, the Netherlands
Authors: Van Schrojenstein Lantman‐de Valk H. M. J. , Wullink M. , Van Den Akker M. , Van Heurn‐Nijsten E. W. A. , Metsemakers J. F. M. , Dinant G. J.
Published: September 2005

Background  Current changes in care philosophy and diversity in care arrangements caused the need for a new estimate of the number of people with intellectual disability (ID), based on recent data. Previous estimates were based on client registrations, which was thought unreliable at this time. This manuscript studies the question how many people with ID can be found in (part of) the Netherlands.

Methods  Identification of people with ID through a combination of general practice (GP) data bases and service registrations in the province of Limburg.

Results  The prevalence of people with ID appeared to be between 0.64% and 0.70%. About 0.21–0.27% were living with family or on their own; 55% of them did not use common ID services.

Conclusion  Results are based on a combination of identification methods. Thirteen per cent of uncertain cases led to minimum and maximum estimates of the population. Limitations of the method and alternative ways of data collection are discussed.
Formalin Attenuates the Stress‐Induced Increase in Plasma Epinephrine Levels
Authors: Mravec B. , Bodnar I. , Uhereczky G. , Nagy G. M. , Kvetnansky R. , Palkovits M.
Published: September 2005

Subcutaneous (s.c.) injection of formalin into rats is frequently used as a painful stressor that produces a three‐phase nociceptive response. We have shown previously that s.c. administered formalin (0.2 ml of 4% solution per 100 g body weight) unexpectedly attenuated the increase of plasma epinephrine levels in rats exposed to exteroceptive stressors (handling, immobilisation). To clarify the mechanism(s) responsible for this phenomenon, the effect of formalin applications on epinephrine plasma levels was investigated in various experimental conditions. Subcutaneous application of formalin combined with exposures of animals to an interoceptive stressor, insulin‐induced hypoglycaemia, significantly attenuated the stress‐induced increase in plasma epinephrine levels, whereas plasma norepinephrine levels remained highly elevated. Moreover, administration of formalin to unstressed animals also manifested signs of an attenuated epinephrine secretion. Interestingly, intraperitoneal administration of formalin did not reduce the elevated levels of plasma epinephrine. We suggest that formalin attenuates epinephrine secretion from the adrenal medulla most probably via irritation of s.c. somatosensory receptors. We hypothesise that the irritation of the primary sensory afferents fibres might reduce the activity of the sympathetic preganglionic neurones innervating adrenal medullary chromaffin cells. Further investigations are required to establish whether the observed reduction of epinephrine secretion from the adrenal medulla is controlled by either spinal or supraspinal neuronal circuits.
Regulation of immune response by Plasmodium‐infected red blood cells
Authors: NDUNGU F. M. , URBAN B. C. , MARSH K. , LANGHORNE J.
Published: September 2005

During the asexual blood stage infection of the human malaria parasite, Plasmodium falciparum, parasite‐derived proteins are inserted onto the surface of the host red blood cell membrane. These proteins are highly variable and were originally thought only to mediate antigenic variation, and sequestration of parasites from peripheral circulation, thus enabling immune evasion. Recent studies have revealed that PfEMP‐1 and other molecules on the P. falciparum‐infected red blood cell (PfRBC) activate and modulate the immune response. In this review, we discuss how PfRBCs interact with antigen‐presenting cells (APCs) and other cells of the immune system, and how such interactions could modulate the host response to Plasmodium infections.
Modulation of the host's immune response by schistosome larvae
Authors: JENKINS S. J. , HEWITSON J. P. , JENKINS G. R. , MOUNTFORD A. P.
Published: September 2005

Schistosomes appear to have evolved several strategies to down‐regulate the host's immune response in order to promote their own survival. For the host, down‐regulation is also beneficial as it can limit the extent of pathology. It is widely accepted that schistosomes modulate the immune response during the chronic phase of infection after egg deposition has started. However, there is increasing evidence that modulation of the immune response can occur much earlier at the time infective cercariae penetrate the host skin. In this review, we explore the various lines of evidence that excretory/secretory (ES) molecules from cercariae down‐regulate the host's immune response. We highlight the immunological factors that are produced and may be involved in regulating the immune system (e.g. IL‐10, and eicosanoids), as well as speculating on possible mechanisms of immune modulation (e.g. mast‐cell activation, T‐cell apoptosis, and/or the skewed activation of antigen‐presenting cells [APCs]). Finally, we draw attention to several molecules of schistosome origin that have the potential to stimulate the regulatory response (e.g. glycans) and link these to potential host receptors (e.g. TLRs and C‐type lectins).
Regulation of innate and acquired immunity in African trypanosomiasis
Authors: MANSFIELD J. M. , PAULNOCK D. M.
Published: September 2005

African trypanosomes are well known for their ability to avoid immune elimination by switching the immunodominant variant surface glycoprotein (VSG) coat during infection. However, antigenic variation is only one of several means by which trypanosomes manipulate the immune system of their hosts. In this article, the role of parasite factors such as GPI anchor residues of the shed VSG molecule and the release of CpG DNA, in addition to host factors such as IFN‐γ, in regulating key aspects of innate and acquired immunity during infection is examined. The biological relevance of these immunoregulatory events is discussed in the context of host and parasite survival.
Immunomodulation by filarial nematodes
Authors: HOERAUF A. , SATOGUINA J. , SAEFTEL M. , SPECHT S.
Published: September 2005

In order to chronically infect their hosts, filarial nematodes have generated a range of strategies to evade and down‐modulate the host's immune system. The recent concept of suppression of immune responses by regulatory T cells has in part benefited from examinations in human and murine filariasis. Its further development in basic immunology animal models has in turn helped to better understand down‐regulatory immune mechanisms in filariasis. Thus, filarial nematodes orchestrate down‐regulation by inducing regulatory T cells and alternatively activated macrophages, which are able to suppress both Th1 and Th2 responses. Regulatory T cells can also induce the secretion of IgG4 from B cells as another arm of modulation. Dendritic cells are down‐regulated upon first encounter with infective L3 larvae. Failure to respond to down‐regulatory induction is based on genetic traits in hosts and leads to reduced parasite loads, albeit at the expense of pathology and disease. Since down‐regulation in chronically and heavily infected hosts extends to third‐party antigens, it is essential to analyse the impact of filarial infection for vaccination, allergy and important coinfections such as malaria, in order to foresee and avert potentially disastrous consequences of filariasis control programmes.
Natural Killer‐Cell Cytotoxicity in HIV‐Positive and HIV‐Negative Patients with and Without Severe Course of Hepatitis B Virus Infection
Authors: Morsica G. , Tasca S. , Biswas P. , Galli A. , Malnati M. , Paties C. , Marinelli M. , Bagaglio S. , Lazzarin A. , Fortis C.
Published: September 2005

Natural killer (NK) cells represent the first line of defence against viral infections but, in the case of hepatitis B virus (HBV), may also be involved in liver injury. We here compared NK‐cell activity of 11 patients with acute HBV infection, either HIV‐positive or HIV‐negative, with that of 11 healthy subjects. One of the HIV‐positive patients, characterized by a severe immunodeficiency, died 3 weeks after hospitalization for HBV‐related fulminant hepatitis (FH). He displayed a remarkable NK‐cell cytotoxicity against both cell lines and autologous dendritic cells, whereas the NK‐cell activity of the remaining patients was significantly reduced as compared with healthy individuals. Our findings suggest that NK‐cell‐mediated cytotoxicity could contribute to the development of HBV‐related acute liver failure in HIV‐positive patients with severe immunodeficiency. An immunopathological model of FH in immunocompromised patients was proposed.
Tobacco BY‐2 cells expressing fission yeast cdc25 bypass a G2/M block on the cell cycle
Authors: Orchard Craig B. , Siciliano Ilario , Sorrell David A. , Marchbank Angela , Rogers Hilary J. , Francis Dennis , Herbert Robert J. , Suchomelova Petra , Lipavska Helena , Azmi Abdelkrim , Onckelen Harry Van
Published: September 2005

The mitotic inducer gene from Schizosaccharomyces pombe, Spcdc25, was used as a tool to investigate regulation of G2/M in higher plants using the BY‐2 (Nicotiana tabacum) cell line as a model. Spcdc25‐expressing BY‐2 cells exhibited a reduced mitotic cell size through a shortening of the G2 phase. The cells often formed isodiametric double files both in BY‐2 cells and in cell suspensions derived from 35S::Spcdc25 tobacco plants. In Spcdc25‐expressing cells, the tobacco cyclin‐dependent kinase, NtCDKB1, showed high activity in early S phase, S/G2 and early M phase, whereas in empty vector cells CDKB1 activity was transiently high in early S phase but thereafter remained lower. Spcdc25‐expressing cells also bypassed a block on G2/M imposed by the cytokinin biosynthetic inhibitor lovastatin (LVS). Surprisingly, cytokinins were at remarkably low levels in Spcdc25‐expressing cells compared with the empty vector, explaining why these cells retained mitotic competence despite the presence of LVS. In conclusion, synchronised Spcdc25‐expressing BY‐2 cells divided prematurely at a small cell size, and they exhibited premature, but sustained, CDKB1 activity even though endogenous cytokinins were virtually undetectable.
Basal resistance against bacteria in Nicotiana benthamiana leaves is accompanied by reduced vascular staining and suppressed by multiple Pseudomonas syringae type III secretion system effector proteins
Authors: Oh Hye‐Sook , Collmer Alan
Published: September 2005

Basal resistance in plants is induced by flagellin and several other common bacterial molecules and is implicated in the immunity of plants to most bacteria and other microbes. However, basal resistance can be suppressed by effector proteins that are injected by the type III secretion system (TTSS) of pathogens such as Pseudomonas syringae. This study demonstrates that basal resistance in the leaves of Nicotiana benthamiana is accompanied by reduced vascular flow into minor veins. Reduced vascular flow was assayed by feeding leaves, via freshly excised petioles, with 1% (weight in volume, w/v) neutral red (NR) and then observing differential staining of minor veins or altered levels of extractable dye in excised leaf samples. The reduced vascular staining was localized to tissues expressing basal resistance and was observable when resistance was induced by either the non‐pathogen Pseudomonas fluorescens, a TTSS‐deficient mutant of P. syringae pv. tabaci, or flg22 (a flagellin‐derived peptide elicitor of basal resistance). Nicotiana benthamiana leaf areas expressing basal resistance no longer elicited the hypersensitive response when challenge inoculated with P. syringae pv. tomato DC3000. The reduced vascular staining effect was suppressed by wild‐type P. syringae pv. tabaci and P. fluorescens heterologously expressing a P. syringae TTSS and AvrPto1PtoJL1065. TTSS‐proficient P. fluorescens was used to test the ability of several P. syringae pv. tomato DC3000 effectors for their ability to suppress the basal resistance‐associated reduced vascular staining effect. AvrEPtoDC3000, HopM1PtoDC3000 (formerly known as HopPtoM), HopF2PtoDC3000 (HopPtoF) and HopG1PtoDC3000 (HopPtoG) suppressed basal resistance by this test, whereas HopC1PtoDC3000 (HopPtoC) did not. In summary, basal resistance locally alters vascular function and the vascular dye uptake assay should be a useful tool for characterizing effectors that suppress basal resistance.
The experience of older people of entering into the phase of asking for public home help – a qualitative study
Authors: Janlöv Ann‐Christin , Rahm Hallberg Ingalill , Petersson Kerstin
Published: September 2005

The aim of this qualitative study was to explore older persons’ (n = 28, 75–96 years of age) experience of becoming in need of public home help, their experience of participation and of having influence on the needs assessment procedure and the decisions made about public home help. A content analysis revealed a broad overarching category, labelled:experiencing discontinuity in life as a whole – the countdown has begun. In addition, four principal categories emerged from the data: comparing the past with the present and losing parts of oneself and connectedness; worrying about the losses and what they will bring about; struggling against losing abilities to avoid dependency and home help; and struggling with conflicting feelings about being/becoming in need of help, and from whom. That older people can so perceive their life situation needs to be recognised if they are to be empowered to become involved in and exert influence on the assessment process and its outcome as well as on their life situation as a whole.
Lupine inhalation induced asthma in a child
Authors: Moreno‐Ancillo Álvaro , Gil‐Adrados Ana C. , Domínguez‐Noche Carmen , Cosmes Pedro M.
Published: September 2005

The ingestion of lupine seed flour has been reported as a cause of allergic reactions. There is some evidence of its allergenic potential after inhalation. An 8‐year‐old asthmatic child, who was allergic to peanut, was studied in our clinic with the suspicion of an adverse drug reaction due to salbutamol. He suffered an asthma attack while playing with his brother, who had been eating lupine seed as snack; surprisingly, the asthma attack worsened with salbutamol. The skin tests showed a positive result with Lupinus albus extract, peanut, garbanzo bean, navy bean, pea, green bean, lentil, soy, Olea europea pollen, grass pollen and Plantago lanceolata pollen. The prick‐by‐prick tests both from dried seeds and those preserved in salt and water were strongly positive. Serum specific IgE antibodies were positive to Lupine albus (1.43 kU/l), peanut (4.32 kU/l), soy (2.15 kU/l), lentil (3.12 kU/l) and garbanzo (0.7 kU/l). After informed consent salbutamol was well tolerated but the patient had asthma in 5 min of manipulation of the lupine seeds. In our case, reactivity with other legumes was also demonstrated, but only peanut allergy was relevant because boiled legumes were tolerated. It is also notorious that anamnesis is so important to assess the true etiological agents of asthma.
Renal function following liver transplantation in children
Authors: Fine Richard N.
Published: September 2005

Abstract: The literature regarding the etiology and incidence of short and long‐term renal functional impairment in pediatric liver allograft recipients was reviewed. Most of the reports include recipients receiving cyclosporine as the primary immunosuppressant. Using calculated glomerular filtration rate (cGFR), creatinine clearance or the serum creatinine level will lead to an overestimation of GFR. In contrast to data in adults, there are a limited number of pediatric recipients whose renal dysfunction has progressed to chronic kidney disease or end‐state renal disease. Calcineurin inhibitors minimization has proven effective in reversing or preventing progressive deterioration of GFR; however, rejection episodes and complications have limited efficacy of this approach. Future multicenter studies using optimal GFR measurements are required to delineate the magnitude of renal dysfunction in pediatric recipients.
Reductions in cholesterol and synaptic markers in association cortex in mood disorders
Authors: Beasley Clare L , Honer William G , von Bergmann Klaus , Falkai Peter , Lütjohann Dieter , Bayer Thomas A
Published: September 2005

Objectives:  Cholesterol forms an integral part of cell membranes and is a major component of myelin. Furthermore, cholesterol also plays a vital role in the development, function and stability of synapses. While low serum cholesterol has previously been associated with mood disorders, cholesterol levels have yet to be quantified within the brain in these disorders. The aim of this study was to quantify sterol levels in the brains of patients with major psychiatric disorders and further to relate these levels to markers of myelin and synapses.

Methods:  Samples of visual association cortex were obtained postmortem from subjects with bipolar disorder (BPD), major depressive disorder (MDD) and schizophrenia (SCZ) and from controls (all n = 15). Concentrations of brain cholesterol, its precursors lathosterol, desmosterol and lanosterol and its metabolite 24S‐hydroxycholesterol were determined by gas‐liquid chromatography. Immunoreactivity for myelin basic protein (MBP), synaptophysin and VAMP was quantified by enzyme‐linked immunosorbent assay.

Results:  Cholesterol levels were 13% lower in MDD (p = 0.018) and 10% lower in BPD (p = 0.052) compared with controls. Cholesterol precursor or metabolite concentrations did not differ between groups. Synaptophysin immunoreactivity was 20% lower in BPD (p = 0.025) and VAMP immunoreactivity 37% lower in MDD (p = 0.032) and 45% lower in BPD (p = 0.009). MBP immunoreactivity was not altered in any disorder.

Conclusions:  Our data suggest that lower brain cholesterol levels and a reduction in synapses may be features of mood disorders.
Zotepine loading in acute and severely manic patients: a pilot study
Authors: Amann Benedikt , Sterr Andrea , Mergl Roland , Dittmann Sandra , Seemüller Florian , Dobmeier Matthias , Orth Michael , Schaefer Martin , Grunze Heinz
Published: September 2005

Objectives:  In clinical practice patients with severe mania (agitation, insomnia and aggressive behaviour) still receive effective, but often not well tolerated typical antipsychotics. The aim of this study was to test the first‐generation atypical antipsychotic zotepine regarding its antimanic efficacy, tolerability and to find an adequate dosage for a loading strategy.

Method:  Twelve patients (seven male) with an acute and severe manic episode, according to DSM‐IV, received zotepine loading in individual dosages (up to 600 mg/day) over a maximum period of 3 weeks. Clinical efficacy was measured using the Young‐Mania Rating Scale (Y‐MRS) total score. Response was defined as a 50% reduction in the Y‐MRS score. Safety was assessed by systematic collection of data on side effects and weight; Hamilton Rating Scale for Depression (HAM‐D) scores were used to detect a switch into depression.

Results:  Two patients dropped out of the study after 2 days. Nine of ten patients (baseline mean Y‐MRS: 45 ± 7) were classified as responders, with five of them responding within 4 days. One patient did not respond sufficiently. No switch into a depressive episode occurred.

Conclusions:  This open pilot study suggests that zotepine with a median daily dosage of 250 mg/day is effective with a rapid therapeutic effect in severely manic patients. In general, patients tolerated the drug well; dose‐dependent extrapyramidal side effects, an increase in weight and autonomic side effects occurred to a lesser degree. This is the first study assessing zotepine monotherapy in manic patients. Controlled studies are warranted.
Which clinical factors predict response to prophylactic lithium? A systematic review for bipolar disorders
Authors: Kleindienst N , Engel RR , Greil W
Published: September 2005

Objectives:  The aim of this study was to systematically integrate the available evidence on response prediction to prophylactic lithium based on clinical factors.

Methods:  Each clinical variable that was related to lithium response in at least one prior study was examined with respect to response prediction. If several studies were located for the same variable, results were integrated using the meta‐analytic approach as suggested by DerSimonian and Laird which was developed for substantial heterogeneity in primary studies.

Results:  Of 42 potential clinical predictors investigated, five variables were identified as possible response predictors of prophylactic lithium: [1] An episodic pattern of mania‐depression‐interval, and [2] a high age of illness onset were identified as potentially protective against a recurrence under lithium. [3] A high number of previous hospitalizations, [4] an episodic pattern of depression‐mania‐interval, and [5] continuous cycling were identified as potential risk factors. Six further variables were found to be significantly related to lithium response, though calculation of fail‐safe numbers indicates that current evidence is not sufficient to hold these variables as reliable predictors of lithium response. All effect‐sizes relating clinical predictors to response were small to moderate.

Conclusions:  Although a few variables are quite robustly supported as response‐predictors in this review, a more in‐depth analysis of each potential predictor is needed. As none of the potential predictors had a very strong impact on response, prediction of lithium response should be based on a multitude of variables.
Evidence that acute hyperinsulinaemia increases the cytokine content in essential organs after an endotoxin challenge in a porcine model
Authors: Brix‐Christensen V. , Vestergaard C. , Andersen S. K. , Krog J. , Andersen N. T. , Larsson A. , Schmitz O. , Tønnesen E.
Published: September 2005

Background:  Insulin has anti‐inflammatory effects, as evaluated by its ability to reduce the plasma concentrations of cytokines. However, the inflammatory processing at the organ level is far less well established. The cytokine content in several organs after endotoxin (lipopolysaccharide, LPS) exposure and the effect of hyperinsulinaemia was examined.

Methods:  Pigs (35–40 kg) were randomized into four groups, anaesthetized and mechanically ventilated for 570 min: group 1 (anaesthesia only; n = 10), group 2 (hyperinsulinaemic euglycaemic clamp, HEC; n = 9), group 3 (LPS; n = 10) and group 4 (LPS + HEC; n = 9). LPS was infused intravenously for 180 min (total dosage, 10 µg/kg). At the end of the study, i.e. 330 min after the termination of LPS or equivalent, cytokine mRNA and cytokine protein contents in the lungs, heart, liver, adipose tissue and spleen were measured.

Results:  Hyperinsulinaemia led to increased interleukin‐10 (IL‐10) protein content in the heart and liver (by 40% and 28%, respectively) in comparison with normoinsulinaemic animals (P < 0.01 and P = 0.02, respectively), and increased tumour necrosis factor‐α (TNF‐α) protein content in the heart (P = 0.02). Animals exposed to LPS exhibited reduced TNF‐α, IL‐6 and IL‐8 protein content in the heart (P = 0.02, P < 0.001 and P = 0.01, respectively). In the kidneys and adipose tissue, a particularly large cytokine protein content was observed.

Conclusion:  The findings strongly substantiate the role of insulin as an immune‐modifying hormone at organ level during baseline and after an endotoxin challenge. Moreover, the kidneys and adipose tissue appear to be pivotal organs in terms of cytokine content shortly after endotoxin exposure, but the complexity remains to be clarified.