bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mercury exposure as a model for deviation of cytokine responses in experimental Lyme arthritis: HgCl2 treatment decreases T helper cell type 1-like responses and arthritis severity but delays eradication ofBorrelia burgdorferiin C3H/HeN mice
Authors: Ekerfelt C , Andersson M , Olausson A , Bergström S , Hultman P 
Published: August 2010

SummaryLyme borreliosis is a complex infection, where some individuals develop so-called ‘chronic borreliosis’. The pathogenetic mechanisms are unknown, but the type of immune response is probably important for healing. A strong T helper cell type 1 (Th1)-like response has been suggested as crucial for eradication of Borrelia and for avoiding development of chronic disease. Many studies aimed at altering the Th1/Th2 balance in Lyme arthritis employed mice deficient in cytokine genes, but the outcome has not been clear-cut, due possibly to the high redundancy of cytokines. This study aimed at studying the importance of the Th1/Th2 balance in murine Borrelia arthritis by using the Th2-deviating effect of subtoxic doses of inorganic mercury. Ninety-eight C3H/HeN mice were divided into four groups: Borrelia-infected (Bb), Borrelia-infected exposed to HgCl2 (BbHg), controls exposed to HgCl2 alone and normal controls. Mice were killed on days 3, 16, 44 and 65 post-Borrelia inoculation. Arthritis severity was evaluated by histology, spirochaetal load determined by Borrelia culture, IgG2a- and IgE-levels analysed by enzyme-linked immunosorbemt assay (ELISA) and cytokine-secreting cells detected by enzyme-linked immunospot (ELISPOT). BbHg mice showed less severe histological arthritis, but delayed eradication of spirochaetes compared to Bb mice, associated with increased levels of IgE (Th2-induced) and decreased levels of IgG2a (Th1-induced), consistent with a Th2-deviation. Both the numbers of Th1 and Th2 cytokine-secreting cells were reduced in BbHg mice, possibly explained by the fact that numbers of cytokine-secreting cells do not correlate with cytokine concentration. In conclusion, this study supports the hypothesis that a Th1-like response is required for optimal eradication of Borrelia.
Tuberculosis antigen-specific immune responses can be detected using enzyme-linked immunospot technology in human immunodeficiency virus (HIV)-1 patients with advanced disease
Authors: Clark S A , Martin S L , Pozniak A , Steel A , Ward B , Dunning J , Henderson D C , Nelson M , Gazzard B , Kelleher P 
Published: August 2010

Summary
There are limited data on the efficacy of T cell-based assays to detect tuberculosis (TB) antigen-specific responses in immune-deficient human immunodeficiency virus (HIV) patients. The aim of this study is to determine whether TB antigen-specific immune responses can be detected in patients with HIV-1 infection, especially in those with advanced disease (CD4 T cell count &lt; 300 cells/µl). An enzyme-linked immunospot (ELISPOT) assay, which detects interferon (IFN)-γ secreted by T cells exposed to TB antigens, was used to assess specific immune responses in a prospective study of 201 HIV-1-infected patients with risk factors for TB infection, attending a single HIV unit. The performance of the ELISPOT assay to detect TB antigen-specific immune responses is independent of CD4 T cell counts in HIV-1 patients. The sensitivity and specificity of this assay for the diagnosis of active tuberculosis does not differ significantly from values obtained in immunocompetent subjects. The negative predictive value of the TB ELISPOT test is 98·2%. A positive predictive value of 86% for the diagnosis of active tuberculosis was found when the combined number of early secretory antigen target-6 (ESAT-6) and culture filtrate protein-10 (CFP-10) IFN-γ spots to CD4 T cell count ratio was &gt; 1·5. TB antigen-specific immune responses can be detected in HIV patients with low CD4 T cell counts using ELISPOT technology in a routine diagnostic laboratory and is a useful test to exclude TB infection in immune-deficient HIV-1 patients. A combination of TB antigen-specific IFN-γ responses and CD4 T cell counts has the potential to distinguish active tuberculosis from latent infection.
Demonstration of autoantibodies to recombinant human sulphite oxidase in patients with chronic liver disorders and analysis of their clinical relevance
Authors: Preuß B , Berg C , Altenberend F , Gregor M , Stevanovic S , Klein R 
Published: August 2010

SummaryIt has been shown previously that sera from patients with cholestatic liver diseases react with sulphite oxidase (SO) prepared from chicken liver. In order to analyse this reactivity and the clinical relevance of anti-SO antibodies in more detail, we produced human recombinant SO. Human recombinant SO (60 kDa) was expressed in Escherichia coli and applied to enzyme-linked immunosorbent assay and Western blot. Sera from patients with autoimmune liver disorders [primary biliary cirrhosis (PBC) n = 96; autoimmune hepatitis (AIH) n = 77; primary sclerosing cholangitis (PSC) n = 39], and from patients with other hepatic (n = 154) and non-hepatic chronic inflammatory disorders (n = 113) were investigated. Highest incidence and activities of IgG-anti-SO antibodies were observed in PSC patients. Nine of 16 untreated (56%) and four of 23 PSC patients treated with ursodeoxycholic acid (UDCA) (17%) were positive. Antibody activity decreased significantly during UDCA treatment. Five per cent of PBC and 9% of AIH patients, but also 15% of patients with alcoholic liver disease, were IgG anti-SO-positive. In patients with viral hepatitis and non-hepatic disorders they could be hardly detected. Anti-SO antibodies are further anti-mitochondrial antibodies in chronic liver diseases. They occur predominantly in PSC, and UDCA treatment seams to decrease antibody activity. Whether these antibodies are primary or secondary phenomena and whether they are related to the aetiology or pathogenesis, at least in a subgroup of patients with chronic liver diseases, has still to be evaluated.
Clonality analysis of lymphoproliferative disorders in patients with Sjögren's syndrome
Authors: Dong L , Masaki Y , Takegami T , Jin Z-X , Huang C-R , Fukushima T , Sawaki T , Kawanami T , Saeki T , Kitagawa K , Sugai S , Okazaki T , Hirose Y , Umehara H 
Published: August 2010

Summary
The aim of this study was to clarify the nature of the clonal lymphocyte infiltration in Sjögren's syndrome (SS) patients associated with lymphoproliferative disorders. We examined B cell clonality in lymphoproliferative tissues from six primary SS patients associated with lymphoproliferative disorders or lymphoma by cloning and sequencing of the gene rearrangement of the immunoglobulin heavy chain complementarity determining region 3 (IgVH–CDR3). Three patients with sequential observation showed progressional clonal expansion with the presence of the same subclone in different tissues during the course of disease. Among them, one patient developed mucosa-associated lymphoid tissue (MALT) lymphoma in glandular parotid. The other three SS patients concomitant with malignant B cells lymphomas showed different clonal expansion of B cells between nodal sites and salivary glands. The cloanality analysis indicated that monoclonal B cell population could spread from one glandular site to another site during the course of SS, suggesting that the malignant clone may arise from the general abnormal microenvironment, not restricted to the glandular tissue, in some SS patients.
Blockade of protease-activated receptors on T cells correlates with altered proteolysis of CD27 by gingipains ofPorphyromonas gingivalis
Authors: Yun L W P , Decarlo A A , Hunter N 
Published: August 2010

SummaryCysteine proteinases, termed gingipains, of Porphyromonas gingivalis are able to inactivate a broad range of host proteins involved in cellular responses and have been implicated as key virulence factors in the onset and progression of adult periodontitis. In the present study, the high molecular weight Arg-gingipain, RgpA, produced a time- and concentration-dependent hydrolysis of the tumour necrosis factor (TNF)-α receptor family member CD27 on resting T cells. As a consequence of CD27 degradation, a reduction in CD27-ligation dependent co-stimulatory CD40L expression was observed. Concomitantly, RgpA activated the protease-activated receptors (PAR)-1, PAR-2 and PAR-4 and induced CD69 and CD25 expression on T cells, thereby demonstrating T cell activation. The Lys-gingipain Kgp demonstrated a low capacity to degrade CD27 but the ability to affect CD27 expression and biological activity was increased when T cells were pretreated with blocking peptide against PAR-2. CD70, the ligand for CD27 induced on activated B cells, was significantly reduced by RgpA treatment and weakly affected by Kgp. These findings suggest that while RgpA can activate T cells through PARs, the parallel action of direct hydrolysis of membrane CD27 as well as CD70 indicates a potential down-regulatory effect through inhibition of CD27/CD70-mediated cell activation in periodontitis.
Activation of granulocytes by direct interaction with dendritic cells
Authors: Tsuda M , Inaba M , Sakaguchi Y , Fukui J , Ueda Y , Omae M , Ando Y , Mukaide H , Guo K , Yabuki T , Nakatani T , Ikehara S 
Published: August 2010

SummaryGranulocytes from human peripheral blood were co-cultured with conventional dendritic cells (cDC) or plasmacytoid DCs (pDC) to examine the effects of DCs on the activation or function of granulocytes. After co-culture of granulocytes with DCs, expression of the activation markers of granulocytes (CD63 and CD64) was up-regulated, and increased expression of CD50, the activation marker and ligand for CD209 (DC-SIGN) was also observed. The interaction of granulocytes with DCs was visualized as the cluster where DCs, especially cDCs, were surrounded by granulocytes to form a ‘rosette’. After co-culture of granulocytes with cDCs, the secretion of elastase from granulocytes was enhanced significantly when examined cytohistochemically and by enzyme-linked immunosorbent assay. An increase in myeloperoxidase (another activation index of granulocytes) was also observed after co-culture with DCs. These findings suggest the functional and phenotypical activation of granulocytes by interaction with DCs. Furthermore, we examined the involvement of adhesion molecules in the granulocyte–DC interaction, and found that CD209 participates to some extent in this interaction.
Serotonin modulates the cytokine network in the lung: involvement of prostaglandin E2
Authors: Ménard G , Turmel V , Bissonnette E Y 
Published: August 2010

SummarySerotonin, well known for its role in depression, has been shown to modulate immune responses. Interestingly, the plasma level of serotonin is increased in symptomatic asthmatic patients and the use of anti-depressants, known to reduce serotonin levels, provokes a decrease in asthma symptoms and an increase in pulmonary function. Thus, we tested the hypothesis that serotonin affects alveolar macrophage (AM) cytokine production, altering the cytokine network in the lung and contributing to asthma pathogenesis. AMs were treated with different concentrations of serotonin (10-11−10-9 M) or 5-HT1 and 5-HT2 receptor agonists for 2 h prior stimulation. T helper 1 (Th1) and Th2 cytokines, prostaglandin-E2 (PGE2) and nitric oxide (NO) were measured in cell-free supernatants. Serotonin significantly inhibited the production of tumour necrosis factor (TNF) and interleukin (IL)-12, whereas IL-10, NO and PGE2 production were increased. These immunomodulatory effects of serotonin were mimicked by 5-HT2 receptor agonist but were not abrogated by 5-HT2 receptor antagonist, suggesting the implication of other 5-HT receptors. Inhibitors of cyclooxygenase and antibody to PGE2 abrogated the inhibitory and stimulatory effect of serotonin on TNF and IL-10 production, respectively, whereas NO synthase inhibitor eliminated serotonin-stimulated IL-10 increase. Furthermore, PGE2 significantly increased AM IL-10 and NO production. These results suggest that serotonin alters the cytokine network in the lung through the production of PGE2. The reduction of Th1-type cytokine by serotonin may contribute to asthma pathogenesis.
Differential response of human naive and memory/effector T cells to dendritic cells infected by respiratory syncytial virus
Authors: Rothoeft T , Fischer K , Zawatzki S , Schulz V , Schauer U , Körner Rettberg C 
Published: August 2010

SummaryIn vitro studies have contributed substantially to the understanding of immunopathology of respiratory syncytial virus (RSV)-mediated disease. In the present study we compared the effect of RSV-infected dendritic cells on the time–course of the primary and memory/effector T cell response in vitro. Cultures with uninfected dendritic cells known to elicit T helper 2 (Th2) responses and with polyinosinic-polycytidylic acid (poly-IC)-stimulated dendritic cells known to elicit Th1 responses served as controls. At day 1 after stimulation there was a high proportion of interleukin (IL)-2 and tumour necrosis factor (TNF)-α-producing T cells with no difference in number of producing T cells as well as concentration of secreted cytokines between RSV-infected and control cultures. However, up to day 3 generation of IFN-γ was reduced markedly. In addition, there was a reduced proliferation in RSV cultures. At day 7 the RSV-treated cultures showed a preponderance of IL-4 generation. At days 21–24, after three rounds of restimulation, memory/effector T cells matured under the influence of RSV were still not fully polarized but in contrast to the primary response displayed a predominance of Th1 cytokines. Contact with RSV-infected HEp-2 cells inhibited proliferation of T cells; memory effector T cells were less sensitive to contact inhibition than naive T cells. In addition, RSV inhibited the stimulated rearrangement of cortical actin more effectively in naive compared to memory T cells. In summary, we have shown that RSV infection of dendritic cells has a distinct modulatory effect on the primary response and a less pronounced effect on the memory response.
Gluten affects epithelial differentiation-associated genes in small intestinal mucosa of coeliac patients
Authors: Juuti-Uusitalo K , Mäki M , Kainulainen H , Isola J , Kaukinen K 
Published: August 2010

Summary
In coeliac disease gluten induces an immunological reaction in genetically susceptible patients, and influences on epithelial cell proliferation and differentiation in the small-bowel mucosa. Our aim was to find novel genes which operate similarly in epithelial proliferation and differentiation in an epithelial cell differentiation model and in coeliac disease patient small-bowel mucosal biopsy samples. The combination of cDNA microarray data originating from a three-dimensional T84 epithelial cell differentiation model and small-bowel mucosal biopsy samples from untreated and treated coeliac disease patients and healthy controls resulted in 30 genes whose mRNA expression was similarly affected. Nine of 30 were located directly or indirectly in the receptor tyrosine kinase pathway starting from the epithelial growth factor receptor. Removal of gluten from the diet resulted in a reversion in the expression of 29 of the 30 genes in the small-bowel mucosal biopsy samples. Further characterization by blotting and labelling revealed increased epidermal growth factor receptor and beta-catenin protein expression in the small-bowel mucosal epithelium in untreated coeliac disease patients compared to healthy controls and treated coeliac patients. We found 30 genes whose mRNA expression was affected similarly in the epithelial cell differentiation model and in the coeliac disease patient small-bowel mucosal biopsy samples. In particular, those genes involved in the epithelial growth factor-mediated signalling pathways may be involved in epithelial cell differentiation and coeliac disease pathogenesis. The epithelial cell differentiation model is a useful tool for studying gene expression changes in the crypt–villus axis.
Reactive nitrogen intermediates and monokines induce caspase-3 mediated macrophage apoptosis by anaerobically stressed Salmonella typhi
Authors: Chanana V , Ray P , Rishi D B , Rishi P 
Published: August 2010

Summary
A successful pathogen manipulates its host for its own benefit. After ingestion, on reaching the intestine Salmonella encounters the resident tissue macrophages. Rather than being destroyed by these professional phagocytes after internalization, Salmonella survives intracellularly. Invasive Salmonella has been reported to induce apoptosis of macrophages as a part of its infection process, which may allow it to avoid detection by the innate immune system. However, the induction of apoptosis under different host environments, including the anaerobic stress encountered by the pathogen in the gut, remains to be examined. The present study is aimed at investigating the apoptotic potential of S. enterica serovar Typhi (S. typhi) grown under anaerobic conditions simulating the in vivo situation encountered by the pathogen. Apoptotic cell death was determined by assessment of nucleosomal DNA and flow cytometric analysis. Evaluation of the data revealed that anaerobically grown S. typhi could induce apoptosis in significantly more number of macrophages compared to the bacterial cells grown under aerobic conditions. A significantly enhanced generation of reactive nitrogen intermediates and caspase-3 activity during macrophage apoptosis induced by anaerobic S. typhi correlated with the increased generation of tumour necrosis factor-α, interleukin (IL)-1α and IL-6. The results indicate that reactive nitrogen intermediates and monokines induce caspase-3 mediated apoptosis of macrophages by S. typhi under anaerobic conditions. These findings may be relevant for clearer understanding of the Salmonella–macrophage interactions and may be of clinical importance in the development of preventive intervention against the infection.
Grasshoppers alter jumping biomechanics to enhance escape performance under chronic risk of spider predation
Authors: Hawlena Dror , Kress Holger , Dufresne Eric R. , Schmitz Oswald J. 
Published: August 2010

Summary1. Prey can increase the probability of escaping a predator attack by adopting either behavioural tactics that provide more time or less distance to escape or by increasing their escape performances. It is assumed that the ability to improve escape performances is reserved for species that respond to chronic predation risk by substantially altering morphological traits related to locomotion. This thinking is at odds with fundamental predictions of physiological stress theory that suggest performance should be enhanced both independently of and in addition to morphological change.2. The purpose of this study was to determine whether and how prey raised under chronic risk of predation can improve their escape performance independent of conspicuous morphological changes.3.  We reared herbivore grasshopper in field mesocosms with and without disarmed hunting spiders and measured their outdoor jumping performance. Grasshoppers were then transferred to the laboratory where we measured the biomechanics of their jumping to elucidate mechanisms that differentiate performance between rearing treatments. We collected second generation nymphal offspring from the field mesocosms and measured their morphology and escape performances to reveal costs associated with antipredator responses.4. Chronically scared grasshoppers made adjustments in jumping technique that enabled them to take‐off 1·2 times faster, which, in combination with additional in‐flight behavioural adjustments, led to 2·6 times longer jump distances. These improvements were independent of conspicuous morphological changes but were accompanied by attendant costs: grasshoppers reared in risky environments produced smaller and less athletic offspring than grasshoppers from risk free environments.5. The results suggest that prey do not need to undergo conspicuous morphological changes in locomotor traits before they can improve escape performance, revealing an adaptive and possibly common aspect of physiological stress reaction to predation.
Tacit definitions of informal caregiving
Authors: Wrubel Judith , Richards T. Anne , Folkman Susan , Acree Michael C. 
Published: August 2010

Tacit definitions of informal caregiving Aims of the study: This study describes three tacit definitions of informal caregiving and explores the extent to which differences in these tacit definitions explain variation in caregivers’ negative mood over time. Background/Rationale: There is a growing need to understand the sources of stress and gratification for informal caregivers. Tacit definitions of informal caregiving refer to caregivers’ understanding of what caregiving entails. These definitions are tacit because they arise from caregivers’ taken‐for‐granted understanding rather than formally articulated positions concerning caregiving. Design/Methods: A random sample of 60 men, all of whom were caregiving partners of men with acquired immunodeficiency syndrome (AIDS), was drawn from a larger cohort of 253 participants in the University of California San Francisco (UCSF) Coping Project (1990–1997). The caregivers were assessed bimonthly for 2 years with procedures that included a semi‐structured interview focusing on a recent stressful event involving caregiving, and quantitative measures of well‐being. Results/Findings: Interpretive phenomenological case studies of the narrative accounts of the 60 caregivers produced three tacit definitions of caregiving – engagement, conflict and distance. These three tacit definitions were distinguished by differences in learning about caregiving, involvement in health care decisions, caregiving activities and reported sources of stress. The three groups differed on measures of dyadic adjustment, depression, anger and anxiety. Conclusions: Better understanding of caregivers’ tacit definitions can facilitate and enhance effective support and interventions for caregivers.
Stressors, coping and depression in haemodialysis patients
Authors: Welch Janet L. , Austin Joan K. 
Published: August 2010

Stressors, coping and depression in haemodialysis patients Background: Depression is common in persons receiving outpatient haemodialysis, but little work has been done to explore the variables associated with depression. Aims: The primary purposes of this study were to (i) examine relationships among stressors, coping and depression and (ii) test the mediating role of coping. Design/Methods: Data were collected at two points in time, three months apart in 1995/1996. The final convenience sample at Time 2 was 86 participants from two United States midwestern, inner‐city dialysis units. Structured interviews were conducted using the Centre for Epidemiologic Studies Depression Scale, the haemodialysis stressor scale (HSS) and the coping strategy indicator. Results: At Time 1 more psychosocial stressors were associated with greater use of problem‐solving, social‐support and avoidance coping. Both avoidance coping and more psychosocial stressors at Time 1 were related to depression at Time 2. Finally, avoidance coping was found to explain much of the relationship between psychosocial stressors and depression. Conclusions: Research is now needed that explicates the causal relationships among stress, coping and depression in haemodialysis patients.