bluuebunny/crossref_metadata_2025_split huggingface dataset:
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

SummaryThe 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

SummaryThe 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.
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

AbstractBackground  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

AbstractSubcutaneous (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

SUMMARY 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

SUMMARY 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

SUMMARY 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

SUMMARY 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

AbstractNatural 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

SummaryThe 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

SummaryBasal 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.
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.