bluuebunny/crossref_metadata_2025_split huggingface dataset:
Several gene programs are induced in ciprofloxacin-treated human lymphocytes as revealed by microarray analysis
Authors: Eriksson Emily , Forsgren Arne , Riesbeck Kristian 
Published: August 2003

Abstract
Fluoroquinolones have immunomodulatory properties and interfere with cytokine production. The aim of this study was to characterize the extent of the superinduced mRNA levels in activated human lymphocytes incubated with ciprofloxacin (5 and 80 μg/ml) using a cytokine gene expression microarray from R&D Systems (Abingdon, UK). Several gene transcripts (n=104) were up-regulated in cells treated with ciprofloxacin at 80 μg/ml, whereas 98 transcripts were down-regulated out of 847 total genes included on the microarray. The increased mRNAs were distributed between major gene programs, including interleukins (36.5%), signal-transduction molecules (13.5%), adhesion molecules (10.6%), tumor necrosis factor and transforming growth factor-β superfamilies (10.6%), cell-cycle regulators (9.6%), and apoptosis-related molecules (8.7%). To determine the specficity of the microarray, a quantitative reverse transcriptase-polymerase chain reaction (RT-PCR), which contained a panel of 12 different cytokine mRNAs, was used. Eleven out of the 12 gene transcripts were up-regulated in the specific RT-PCR, whereas only eight were found to be increased in the microarray. A microarray from Clontech (Hampshire, UK), containing 588 different genes, was also included. Results obtained with this broad-coverage expression array slightly differed compared with the other microarray. We conclude that the fluoroquinolone ciprofloxacin at high concentrations interferes with several gene programs, which is in accordance with a mammalian stress response. From a technical point of view, a discrepancy may exist between data obtained by different microarrays and more specific methods such as quantitative RT-PCR.
Expression of the chemokine IP-10 (CXCL10) by hepatocytes in chronic hepatitis C virus infection correlates with histological severity and lobular inflammation
Authors: Harvey Charles E , Post Jeffrey J , Palladinetti Patricia , Freeman Anthony J , Ffrench Rosemary A , Kumar Rakesh K , Marinos George , Lloyd Andrew R 
Published: August 2003

Abstract
The factors influencing lymphocyte trafficking to the liver lobule during chronic hepaititis C virus (HCV) infection are currently not well defined. Interferon-γ-inducible protein 10 (IP-10), a chemokine that recruits activated T lymphocytes, has recently been shown by in situ hybridization to be expressed in the liver during chronic HCV infection. This study sought to define the cellular source of IP-10 in the liver by immunohistochemistry, to examine the expression of its receptor, CXCR3, on T lymphocytes isolated from blood and liver tissue, and to correlate IP-10 expression with the histological markers of inflammation and fibrosis. IP-10 was expressed by hepatocytes but not by other cell types within the liver, and the most intense immunoreactivity was evident in the areas of lobular inflammation. The IP-10 receptor was expressed on a significantly higher proportion of T lymphocytes in the liver compared with blood. CD8 T lymphocytes, which predominate in the liver lobule, were almost uniformly CXCR3-positive. The expression of IP-10 mRNA correlated with lobular necroinflammatory activity but not with inflammation or fibrosis in the portal tracts. These findings suggest that IP-10 may be induced by HCV within hepatocytes and may be important in the pathogenesis of chronic HCV infection, as recruitment of inflammatory cells into the lobule is an important predictor of disease progression.
Lactobacilli and streptococci induce inflammatory chemokine production in human macrophages that stimulates Th1 cell chemotaxis
Authors: Veckman Ville , Miettinen Minja , Matikainen Sampsa , Lande Roberto , Giacomini Elena , Coccia Eliana M , Julkunen Ilkka 
Published: August 2003

Abstract
Macrophages have a central role in innate-immune responses to bacteria. In the present work, we show that infection of human macrophages with Gram-positive pathogenic Streptococcus pyogenes or nonpathogenic Lactobacillus rhamnosus GG enhances mRNA expression of inflammatory chemokine ligands CCL2/monocyte chemoattractant protein-1 (MCP-1), CCL3/macrophage-inflammatory protein-1α (MIP-1α), CCL5/regulated on activation, normal T expressed and secreted, CCL7/MCP-3, CCL19/MIP-3β, and CCL20/MIP-3α and CXC chemokine ligands CXCL8/interleukin (IL)-8, CXCL9/monokine induced by interferon-γ (IFN-γ), and CXCL10/IFN-inducible protein 10. Bacteria-induced CCL2, CCL7, CXCL9, and CXCL10 mRNA expression was partially dependent on ongoing protein synthesis. The expression of these chemokines and of CCL19 was dependent on bacteria-induced IFN-α/β production. CCL19 and CCL20 mRNA expression was up-regulated by IL-1β or tumor necrosis factor α (TNF-α), and in addition, IFN-α together with TNF-α further enhanced CCL19 gene expression. Synergy between IFN-α and TNF-α was also seen for CXCL9 and CXCL10 mRNA expression. Bacteria-stimulated macrophage supernatants induced the migration of T helper cell type 1 (Th1) cells, suggesting that in human macrophages, these bacteria can stimulate efficient inflammatory chemokine gene expression including those that recruit Th1 cells to the site of inflammation. Furthermore, L. rhamnosus-induced Th1 chemokine production could in part explain the proposed antiallergenic properties of this bacterium.
ADAM-17-independent shedding of L-selectin
Authors: Walcheck Bruce , Alexander Shelia R , St. Hill Catherine A , Matala Erik 
Published: August 2003

Abstract
L-selectin is expressed by leukocytes and facilitates their adhesion under flow along the walls of blood vessels. As do a variety of membrane proteins, L-selectin undergoes ectodomain shedding. Using approaches that monitor full-length L-selectin in short-term assays, it has been determined that L-selectin shedding is defective in tumor necrosis factor α-converting enzyme (ADAM-17)-deficient cells. In this study, we examined the steady-state levels of L-selectin on ADAM-17-deficient cells using a monoclonal antibody to the cytoplasmic region of L-selectin, which allows for the detection of total L-selectin (full-length and the membrane-associated cleavage fragment). We demonstrate that ADAM-17-deficient cells generate a 6-kDa transmembrane fragment of L-selectin. Although inducible L-selctin shedding by phorbol 12-myristate 13-acetate stimulation was not observed by these cells in short-term assays, basal turnover did occur, resulting in the production of soluble L-selectin, as determined by enzyme-linked immunosorbent assay. L-selectin turnover was greatly increased upon ADAM-17 reconstitution. Truncating the juxtamembrane region of L-selectin blocked ADAM-17-independent shedding as did a hydroxymate metalloprotease inhibitor. Together, these findings demonstrate that a metalloprotease activity separate from ADAM-17 can use the cleavage domain of L-selectin. We speculate that separate proteolytic mechanisms of L-selectin shedding may regulate distinct antiadhesive mechanisms, such as inducible shedding for the rapid dissociation of cell–cell interactions and constitutive shedding for the homeostatic maintenance of high serum levels of soluble L-selectin, a potential adhesion buffer.
Nitric oxide-mediated inhibition of caspase-dependent T lymphocyte proliferation
Authors: Mahidhara Raja S , Hoffman Rosemary A , Huang Sulan , Wolf-Johnston Amanda , Vodovotz Yoram , Simmons Richard L , Billiar Timothy R 
Published: August 2003

Abstract
Nitric oxide (NO), a pleiotropic signaling molecule produced at sites of inflammaion, is a powerful inhibitor of lymphocyte proliferation. Caspases, central effector proteases in apoptosis, have recently been implicated as critical mediators of T cell activation. We and others have shown that NO can inhibit caspases by S-nitrosylation, which is reversible by the reducing agent dithiothreitol (DTT). The purpose of the present study was to determine whether NO inhibits lymphocyte proliferation by modulating caspase activity. Caspase inhibition with z-VAD-fmk blocked T cell proliferation. NO-dependent inhibition of T cell proliferation was associated with an inhibition of caspase activity and activation, and this effect was reversible by DTT. Previous studies demonstrated inhibition of apoptosis through S-nitrosylation of caspases; the present studies extend this effect to inhibition of caspase-dependent T cell proliferation.
Enhancement by neutrophils of collagen degradation by corneal fibroblasts
Authors: Li Qin , Fukuda Ken , Lu Ying , Nakamura Yoshikuni , Chikama Tai-ichiro , Kumagai Naoki , Nishida Teruo 
Published: August 2003

Abstract
Activated corneal fbroblasts and infiltrated leukocytes are thought to contribute to corneal ulceration. The potential roles of neutrophil-fibroblast and cell-matrix interactions in the degradation of stromal collagen associated with corneal ulceration have now been investigated with the use of three-dimensional cultures of rabbit cells in collagen gels. Degradation of collagen fibrils during culture was measured by spectrophotometric determination of released hydroxyproline. Whereas corneal fibroblasts alone degraded collagen fibrils to a small extent, neutrophils did not. However, the addition of neutrophils or neutrophil–conditioned medium (CM) to cultures of corneal fibroblasts resulted in a marked increase in the amount of collagen degraded by the fibroblasts. The effect of CM from neutrophils cultured in collagen gels on collagen degradation by corneal fibroblasts was greater than that of medium conditioned by neutrophils in monolayer culture. Immunoblot as well as reverse transcription and real-time polymerase chain reaction analyses revealed that neutrophil–CM stimulated the synthesis of matrix metalloproteinase (MMP)-1 and MMP-3 by corneal fibroblasts. The stimulatory effect of neutrophils on collagen degradation by corneal fibroblasts was inhibited by the synthetic MMP inhibitor ilomastat and by interleukin-1 (IL-1) receptor antagonist. These results suggest that factors secreted by collagen-stimulated neutrophils augment collagen degradation by corneal fibroblasts through a stimulatory effect on MMP synthesis and that IL-1 released by neutrophils may contribute to this effect.
Tracking death dealing by Fas and TRAIL in lymphatic neoplastic disorders: pathways, targets, and therapeutic tools
Authors: Greil Richard , Anether Gabriele , Johrer Karin , Tinhofer Inge 
Published: August 2003

Abstract
In the past decade, it was concluded from a number of investigations that death domain-containing members of the tumor necrosis factor-receptor (TNF-R) family and their ligands such as Fas/FasL and TNF-related apoptosis-inducing ligand (TRAIL)-R/TRAIL are essential for maintaining an intact immune system for surveillance against infection and cancer development and that nondeath domain-containing members such as CD30 or CD40 are involved in the fine tuning of this system during the selection process of the lymphaticsystem. In line with this conclusion are the observations that alterations in structure, function, and regulation of these molecules contribute to autoimmunity and cancer development of the lymphoid system. Besides controlling size and function of the lymphoid cell pool, Fas/FasL and TRAIL-R/TRAIL regulate myelopoiesis and the dendritic cell functions, and severe alterations of these lineages during the outgrowth and expansion of the lymphoid tumors have been reported. It is the aim of this review to summarize what is currently known about the complex role of these two death receptor/ligand systems in normal, disturbed, and neoplastic hemato-/lymphopoiesis and to point out how such knowledge can be used in developing novel, therapeutic options and the problems that will have to be faced along the way.
The polysaccharide capsule of Cryptococcus neoformans interferes with human dendritic cell maturation and activation
Authors: Vecchiarelli Anna , Pietrella Donatella , Lupo Patrizia , Bistoni Francesco , McFadden Diane C , Casadevall Arturo 
Published: August 2003

Abstract
The ability of encapsulated andacapsular strains of Cryptococcus neoformans to activate dendritic cells (DC) derived from monocytes stimulated with granulocyte macrophage-colony stimulating factor and interleukin-4 was evaluated. Profound differences in DC response to encapsulated and acapsular C. neoformans strains were observed. In particular, (i) the acapsular strain was easily phagocytosed by immature DC, and the process induced several molecular markers, such as major histocompatibility complex (MHC) class I and class II, CD40, and CD83, which are characteristic of mature DC; (ii) the encapsulated strain did not up-regulate MHC class I and class II and CD83 molecules; (iii) the soluble capsular polysaccharide glucuronoxylomannan (GXM) is unable to regulate MHC class I and class II molecules; (iv) the addition of monoclonal antibody to GXM (anti-GXM) to the encapsulated strain facilitated antigen-presenting cell maturation by promoting ingestion of C. neoformans via Fc receptor for immunoglobulin G (FcγR)II (CD32) and FcγRIII (CD16); (v) pertubation of FcRγII or FcγRIII was insufficient to promote DC maturation; and (vi) optimal DC maturation permitted efficient T cell activation and differentiation, as documented by the enhancement of lymphoproliferation and interferon-γ production. These results indicate that the C. neoformans capsule interferes with DC activation and maturation, indicating a new pathway by which the fungus may avoid an efficient T cell response.
Phospholipase C and phosphatidylinositol 3-kinase signaling are involved in the exogenous arachidonic acid-stimulated respiratory burst in human neutrophils
Authors: Liu Jiang , Liu Zhaoxia , Chuai Shaokun , Shen Xun 
Published: August 2003

Abstract
To define the role of phospholipase C (PLC) and phosphatidylinositol 3-kinase (PI-3K), signaling pathways in arachidonic acid (AA)-stimulated respiratory burst in human neutrophils, the AA-stimulated respiratory burst, Ins(1,4,5)P3 production, PI-3K activation, and cytoplasmic Ca2+ mobilization were investigated. It was found that Ins(1,4,5)P3 production and PI-3K activity in AA-stimulated cells were increased in a dose-dependent manner. U73122, the PLC inhibitor, effectively inhibited the AA-stimulated respiratory burst and Ca2+ release from th intracellular calcium store but not the activity of PI-3K, indicating the independence of PI-3K signaling on PLC activation. Wortmannin, the PI-3K inhibitor, at the concentration sufficient to inhibit PI-3K activity, can only partially inhibit Ca2+ release from the internal store, indicating a partial regulation of PLC signaling by PI-3K and the existence of two pathways initiated by different PLC subfamilies. One is regulated by PI-3K activation, and the other is independent of PI-3K signaling. It was observed that AA could still induce a noncapacitative Ca2+ entry in the cells when Ca2+ release from the intracellular store was blocked by a PLC inhibitor, or a capacitative Ca2+ entry was induced by preincubation with thapsigargin. However, the AA-mediated, noncapacitative Ca2+ entry seems to play a little, if any, role in the stimulated respiratory burst. The present study suggests that the PLC signaling pathway, which may be activated by PLCβ and PLCγ, respectively, and the PI-3K signaling pathway are involved in the AA-stimulated respiratory burst in human neutrophil.
IL-4 primes human endothelial cells for secondary responses to histamine
Authors: Wierzbicki Tom , Iqbal Shehzad M , Cuvelier Susan L , Awong Geneve , Tibbles Lee Anne , Patel Kamala D 
Published: August 2003

Abstract
Interleukin-4 (IL-4) is a multifunctional cytokine, which is involved in numerous disease states, including atopic asthma. IL-4 not only induces direct responses in cells but can also prime for secondary responses to stimuli. Little is known about the priming effects of IL-4 on endothelial cells; therefore, we chose to examine the ability of IL-4 to prime endothelial cells for platelet-activating factor (PAF) synthesis and prostaglandin E2 (PGE2) release. IL-4 alone did not enhance PAF synthesis or PGE2 release; however, pretreatment with IL-4 primed for PAF synthesis and PGE2 release in response to subsequent stimulation with histamine. In contrast, tumor necrosis factor α (TNF-α), oncostatin M (OSM), and IL-1β did not prime endothelial cells for PAF synthesis in response to histamine. The priming effects of IL-4 occurred without any detectable changes in the requirement for signaling pathways upstream of PGE2 release. IL-4 treatment increased the expression of mRNA for histamine receptor 1 (HR1) and shifted the inhibition curve for pyrilamine, a specific HR1 antagonist. In addition, the dose-response curve for histamine-induced elevations in intracellular calcium was shifted following IL-4 stimulation. Together, these data indicate that HR1 is up-regulated in IL-4-stimulated human umbilical vein endothelial cells (HUVEC) and suggest that this up-regulation may contribute to the enhanced responsiveness of IL-4-stimulated HUVEC to histamine.
Expression and function of chemokines during viral infections: from molecular mechanisms to in vivo function
Authors: Melchjorsen Jesper , Sørensen Louise N , Paludan Søren R 
Published: August 2003

Abstract
Recruitment and activation of leukocytes are important for elimination of microbes, including viruses, from infected areas. Chemokines constitute a group of bioactive peptides that regulate leukocyte migration and also contribute to activation of these cells. Chemokines are essential mediators of inflammation and important for control of viral infections. The profile of chemokine expression contributes to shaping the immune response during viral infection, whereas viral subversion of the chemokine system allows the virus to evade antiviral activities of the host. In this review, we discuss the role of chemokines in host-defense against virus infections, and we also look deeper into the virus-cell interactions that trigger chemokine expression as well as the cellular signaling cascades involved.
LF15-0195 generates tolerogenic dendritic cells by suppression of NF-κB signaling through inhibition of IKK activity
Authors: Yang Jinming , Bernier Suzanne M , Ichim Thomas E , Li Mu , Xia Xiaoping , Zhou Dejun , Huang Xuyan , Strejan Gill H , White David J , Zhong Robert , Min Wei-Ping 
Published: August 2003

AbstractLF15-0195 (LF) is a potent, less toxic analog of the immunosuppressant 15-deoxyspergualine, which we previously reported to prevent graft rejection and to induce permanent tolerance in a murine cardiac transplantation model. However, the underlying mechanism of action of LF required elucidation. In this study, dendritic cells (DC) treated with LF before activation with tumor necrosis factor α (TNF-α)/lipopolysaccharide (LPS) failed to express maturation markers (major histocompatibility complex II, CD40, CD86) and interleukin-12. LF prevented, in a concentration-dependent manner, the activation and nuclear translocation of nuclear factor-κB (NF-κB) in DC following addition of TNF-α/LPS. Yet-activated and active IκB kinases (IKKs) were inhibited in cells pretreated with LF, thereby preventing the phosphorylation of IκB and release of NF-κB, a key regulator of genes associated with the maturation of DC. LF-induced inhibition of IKK activity was reversed in a dose-dependent manner by the overexpression of IKK. The T helper cell type 2 (Th2) differentiation of naïve T cells promoted by LF-treated DC in vitro correlates with Th2 polarization observed in transplant recipients made tolerant by LF. These data demonstrated that LF-induced blockade of NF-κB signaling at the level of IKK promoted the generation of tolerogenic DC that inhibited Th1 polarization and increased Th2 polarization in vitro and in vivo.
Clinical interventions for treatment non-adherence in psychosis: Meta-analysis
Authors: Nosé Michela , Barbui Corrado , Gray Richard , Tansella Michele 
Published: August 2003

BackgroundStudies investigating the efficacy of clinical interventions for reducing treatment non-adherence have generated contrasting findings, and treatment non-adherence remains common in clinical practice.AimsTo systematically review whether there are effective clinical interventions that community psychiatric services can implement to reduce non-adherence.MethodSystematic review and metaregression analysis of randomised controlled trials (RCTs) and controlled clinical trials (CCTs) were used to assess the efficacy of interventions to enhance adherence.ResultsWe reviewed 24 studies, more than half of which were RCTs. In 14 studies the experimental intervention was an educational programme. Five studies evaluated pre-discharge educational sessions, three studies explored the benefit of psychotherapeutic interventions and two studies looked at the effect of telephone prompts. The overall estimate of the efficacy of these interventions produced an odds ratio of 2.59 (95% Cl 2.21–3.03) for dichotomous outcomes, and a standardised mean difference of 0.36 (95% Cl 0.06–0.66) for continuous outcomes.ConclusionsCommunity psychiatric services can potentially use effective clinical interventions, backed by scientific evidence, for reducing patient non-adherence.
Long-term outcome of late-onset schizophrenia: 5-year follow-up study
Authors: Brodaty Henry , Sachdev Perminder , Koschera Annette , Monk Dorothy , Cullen Breda 
Published: August 2003

BackgroundThere is controversy about whether late-onset schizophrenia is a precursor of cognitive decline.AimsTo examine the long-term outcome of a group of patients with late-onset schizophrenia.MethodPatients with onset of DSM–III–R schizophrenia at age 50 years or over, but without dementia, and a healthy control group were assessed at baseline (n=27 and n=34, respectively), after 1 year and after 5 years (n=19 and n=24, respectively) on measures of psychopathology, cognition and general functioning, and compared on rates of decline and incidence of dementia.ResultsNine patients with late-onset schizophrenia and none of the control group were found to have dementia (5 Alzheimer type, 1 vascular, 3 dementia of unknown type) at 5-year follow-up. There appeared to be a subgroup of late-onset schizophrenia patients without signs of dementia at baseline or at 1 year follow-up who subsequently declined.ConclusionsLate-onset schizophrenia may be a prodrome of Alzheimer-type dementia. More longitudinal studies are required to determine its nosological status.
Variations in the costs of child and adolescent psychiatric in-patient units
Authors: Beecham Jennifer , Chisholm Daniel , O'Herlihy Anne , Astin Jack 
Published: August 2003

BackgroundChild and adolescent inpatient care is a highly specialised service, ideally requiring planning at a national level, but there are no routine data collections specifically for these services.AimsTo estimate unit costs for child and adolescent psychiatric in-patient units and to analyse the variations in costs between units.MethodData collection alongside a national survey with cost estimations guided by principles drawn from economic theory. Bivariate and multivariate analyses are employed to identify cost influences.ResultsFifty-eight units could provide sufficient data to allow calculation of the cost per in-patient day; mean=$197 (s.d.=71.6; 1999–2000 prices). The management sector, type of provision, number of rooms, capacity and location explained nearly half of the cost variation.ConclusionsChild and adolescent psychiatric in-patient units are an expensive resource, with personnel absorbing two-thirds of the total costs. Costs per in-patient day vary fourfold and the exploration of cost variations can inform commissioning strategies.