bluuebunny/crossref_metadata_2025_split huggingface dataset:
The use of prophylactic fluconazole in immunocompetent high-risk surgical patients: a meta-analysis
Authors: Ho Kwok M , Lipman Jeffrey , Dobb Geoffrey J , Webb Steven AR 
Published: October 2005

Abstract
Introduction
High-risk surgical patients are at increased risk of fungal infections and candidaemia. Evidence from observational and small randomised controlled studies suggests that prophylactic fluconazole may be effective in reducing fungal infection and mortality. We evaluated the effects of prophylactic fluconazole on the incidence of candidaemia and hospital mortality in immunocompetent high-risk surgical patients.

Methods
Randomised controlled studies involving the use of fluconazole in immunocompetent high-risk surgical patients from the Cochrane Controlled Trial Register (2005, issue 1) and from the EMBASE and MEDLINE databases (1966–30 April 2005), without any language restriction, were included. Two reviewers reviewed the quality of the studies and performed data extraction independently.

Results
Seven randomised controlled studies with a total of 814 immunocompetent high-risk surgical patients were considered. The use of prophylactic fluconazole was associated with a reduction in the proportion of patients with candidaemia (relative risk [RR] = 0.21, 95% confidence interval [CI] = 0.06–0.72, P = 0.01; I2 = 0%) and fungal infections other than lower urinary tract infection (RR = 0.39, 95% CI = 0.24–0.65, P = 0.0003; I2 = 0%), but was associated with only a trend towards a reduction in hospital mortality (RR = 0.82, 95% CI = 0.62–1.08, P = 0.15; I2 = 7%). The proportion of patients requiring systemic amphotericin B as a rescue therapy for systemic fungal infection was lower after prophylactic use of fluconazole (RR = 0.35, 95% CI = 0.17–0.72, P = 0.004; I2 = 0%). The proportion of patients colonised with or infected with fluconazole-resistant fungi was not significantly different between the fluconazole group and the placebo group (RR = 0.66, 95% CI = 0.22–1.96, P = 0.46; I2 = 0%).

Conclusion
The use of prophylactic fluconazole in immunocompetent high-risk surgical patients is associated with a reduced incidence of candidaemia but with only a trend towards a reduction in hospital mortality.
The interferon-inducible gene, Ifi204, is transcriptionally activated in response to M-CSF, and its expression favors macrophage differentiation in myeloid progenitor cells
Authors: Dauffy Jérémy , Mouchiroud Guy , Bourette Roland P 
Published: October 2005

Abstract
The interferon-inducible (Ifi)204 gene was isolated as a macrophage-colony stimulating factor (M-CSF)-responsive gene using a gene trap approach in the myeloid interleukin-3 (IL-3)-dependent FD-Fms cell line, which differentiates in macrophages in response to M-CSF. Here, we show that Ifi204 was transcriptionally activated in response to M-CSF, and FD-Fms cells decreased their growth and committed toward a macrophage morphology; this induction was abrogated when the differentiation signal of the M-CSF receptor was blocked; the Ifi204 gene was also induced during macrophage differentiation controlled by leukemia inhibitory factor; and the Ifi204 gene is expressed in different mature monocyte/macrophage cells. Finally, we showed that enforced expression of Ifi24 strongly decreased IL-3- and M-CSF-dependent proliferation and conversely, favored macrophage differentiation of FD-Fms cells in response to M-CSF. Altogether, these results demonstrate that the Ifi204 gene is activated during macrophage development and suggest that the Ifi204 protein may act as a regulator of the balance between proliferation and differentiation. Moreover, this study suggests that other members of the Ifi family might act as regulators of hematopoiesis under the control of hemopoietic cytokines.
PAF-receptor antagonists, lovastatin, and the PTK inhibitor genistein inhibit H2O2 secretion by macrophages cultured on oxidized-LDL matrices
Authors: Sethy-Coraci Indra , Crock Lara W , Silverstein Samuel C 
Published: October 2005

AbstractAdhesion of mononuclear phagocytes (Macs) to extracellular matrices containing oxidized low-density lipoproteins (oxLDL) stimulates these cells to secrete reactive oxygen species (e.g., O2–, H2O2) that are believed to promote atherogenesis. Current in vitro systems designed to measure Mac H2O2 secretion in response to oxLDL show that these cells secrete H2O2 for only a few hours after plating. The slow onset and chronicity of atherogenesis, however, suggested to us that Mac ROS secretion might be sustained for much longer periods when Macs are maintained in an environment resembling that in the intima of arteries undergoing atherogenesis. The findings reported here confirm this suggestion. They show that Macs maintained on collagen IV matrices containing oxLDL in medium containing human plasma-derived serum secrete H2O2 continuously and in large amounts for at least 11 days. Using this system we tested the effects of compounds known to attenuate atherogenesis in vivo. Platelet-activating factor (PAF) receptor antagonists, lovastatin, and the isoflavone protein tyrosine kinase (PTK) inhibitor genistein each reduced H2O2 secretion by Macs maintained on oxLDL-containing matrices by ∼60%. Lovastatin's inhibitory effect was blocked completely by addition of geranylgeranyl pyrophosphate to the medium. We conclude that matrix-bound and oxidized lipoproteins stimulate Macs to produce H2O2 continuously and in large quantities via a pathway that involves PAF receptors and PTK and is reversibly blocked by inhibitors of protein prenylation.
Modulation of phenotype and function of dendritic cells by a therapeutic synthetic killer peptide
Authors: Cenci Elio , Pericolini Eva , Mencacci Antonella , Conti Stefania , Magliani Walter , Bistoni Francesco , Polonelli Luciano , Vecchiarelli Anna 
Published: October 2005

Abstract
The strong microbicidal effects of an engineered synthetic killer peptide (KP), which functionally mimics a fungal killer toxin, have been demonstrated extensively. β-glucan has been identified as a receptor for KP on fungal cell walls. Although the direct microbicidal and related therapeutic effects have been studied in depth, no information currently exists about the interaction of KP with immune cells. In this study, we exploited the possibility of KP binding to different murine immune cell populations. The results demonstrate that KP binds selectively to dendritic cells (DC) and to a lesser extent, to macrophages but not to lymphocytes and neutrophils; KP binding possibly occurs through major histocompatibility complex (MHC) class II, CD16/32, and cellular molecules recognized by anti-specific intercellular adhesion molecule-grabbing nonintegrin R1 antibodies; and KP modulates the expression of costimulatory and MHC molecules on DC and improves their capacity to induce lymphocyte proliferation. These findings provide evidence that this synthetic KP interacts selectively with DC and modulating their multiple functions, might also serve to improve the immune antimicrobial response.
Endotoxin tolerance induces selective alterations in neutrophil function
Authors: Parker Lisa C , Jones Elizabeth C , Prince Lynne R , Dower Steven K , Whyte Moira K B , Sabroe Ian 
Published: October 2005

AbstractEndotoxin tolerance has the potential to limit phagocyte responses to Toll-like receptor (TLR) agonists, but the role of tolerance in regulating neutrophil responses is unknown. We investigated neutrophil responses to prolonged lipopolysaccharide (LPS) exposure and observed induction of tolerance in intracellular signaling pathways and respiratory burst. These effects were not prevented by granulocyte macrophage-colony stimulating factor (GM-CSF) pretreatment, and tolerized neutrophils retained the ability to respond to GM-CSF and other survival factors with a delay in apoptosis. In addition, LPS-exposed neutrophils showed continued generation of CXC chemokine ligand 8, which was not reduced in tolerized cells. Induction of tolerance was associated with a loss of TLR4 surface expression. Tolerance, therefore, induces a selective reprogramming of neutrophil function, but cells retain a predominantly proinflammatory phenotype.
Synergistic enhancement of cytokine-induced human monocyte matrix metalloproteinase-1 by C-reactive protein and oxidized LDL through differential regulation of monocyte chemotactic protein-1 and prostaglandin E2
Authors: Zhang Yahong , Wahl Larry M 
Published: October 2005

Abstract
C-reactive protein (CRP) and oxidized LDL (ox-LDL) are associated with inflammatory lesions, such as coronary artery disease, in which monocytes and matrix metalloproteinases (MMPs) may play a major role in the rupture of atherosclerotic plaques. Monocytes are recruited to inflammation sites by monocyte chemoattractant protein-1 (MCP-1), which may also participate in the activation of monocytes. The objective of this study was to compare the individual and combined effect of CRP and ox-LDL on human monocyte MMP-1 and the role of MCP-1 in this effect. Although CRP or ox-LDL failed to induce MMP-1 in control monocytes, these molecules enhanced MMP-1 production induced by tumor necrosis factor α (TNF-α) and granulocyte macrophage-colony stimulating factor (GM-CSF) with a synergistic increase in MMP-1 occurring in the presence of both mediators. Enhancement of MMP-1 by CRP and ox-LDL wasattributable to a differential increase in MCP-1 and prostaglandin E2(PGE2). CRP, at physiological concentrations, induced high levels of MCP-1 and relatively low levels of PGE2, whereas ox-LDL caused a significant enhancement of PGE2 with little affect on MCP-1. Accordingly, CRP- and ox-LDL-induced MMP-1 production by monocytes was inhibited by anti-MCP-1 antibodies and indomethacin, respectively. Moreover, addition of exogenous MCP-1 or PGE2 enhanced MMP-1 production by TNF-α- and GM-CSF-stimulated monocytes. These results show that the combination of CRP and ox-LDL can cause a synergistic enhancement of the role of monocytes in inflammation, first, by increasing MCP-1, which attracts more monocytes and directly enhances MMP-1 production by activated monocytes, and second, by elevating PGE2 production, which also leads to higher levels of MMP-1.
Latent TGF-β1-transduced CD4+ T cells suppress the progression of allergic encephalomyelitis
Authors: Murano Mitsuyuki , Xiong Xiaozhong , Murano Naoko , Salzer James L , Lafaille Juan J , Tsiagbe Vincent K 
Published: October 2005

Abstract
Systemic injection of small amounts of transforming growth factor-β (TGF-β), a cytokine produced by lymphoid and other cells, has a profound effect in protecting mice from the nflammatory demyelinating lesions of experimental allergic encephalomyelitis (EAE; an animal model for multiple sclerosis). However, TGF-β has side-effects, which might be avoided if the cells producing TGF-β can be delivered to the affected site in the nervous system to insure its local release in small amounts. Myelin basic protein (MBP)-specific, cloned CD4+ T cells were engineered by retroviral transduction to produce latent TGF-β. Studies about the spontaneous form of EAE in T cell receptor (TCR)-transgenic recombination-activating gene (RAG)-1−/− mice showed that essentially all of the MBP-specific, TCR-transgenic RAG-1−/− (BALB/c×B10.PL)F1 mice develop spontaneous EAE by the age of 11 weeks. By 12 weeks, 25–50% of the mice have died from disease. A single injection of TGF-β1-transduced T helper cell type 1 (Th1) cells significantly protected the mice from EAE, and untransduced Th1 cells did not protect. MBP-specific BALB/c Th2 clones, transduced with TGF-β1-internal ribosome entry site-green fluorescent protein (GFP) significantly reduced EAE induction by untransduced Th1 cells in RAG-1−/− B10.PL mice. Furthermore, the GFP+ TGF-β1-producing Th2 cells were detectable in the spinal cords of the injected mice.
Induction of intracellular calcium elevation by Δ9-tetrahydrocannabinol in T cells involves TRPC1 channels
Authors: Rao Gautham K , Kaminski Norbert E 
Published: October 2005

AbstractWe have reported previously that Δ9-tetrahydrocannabinol (Δ9-THC) treatment of resting human and murine splenic T cells robustly elevated intracellular calcium ([Ca2+]i). The objective of the present investigation was to examine the putative role of [Ca2+]i store depletion and store-operated calcium (SOC) [1] and receptor-operated cation (ROC) channels in the mechanism by which Δ9-THC increases [Ca2+]i in the cannabinoid-2 receptor-expressing human peripheral blood-acute lymphoid leukemia (HPB-ALL) human T cell line. By using the smooth endoplasmic reiculum Ca2+-ATPase pump inhibitor, thapsigargin, and the ryanodine receptor antagonist, 8-bromo-cyclic adenosine diphosphate ribose, we demonstrate that the Δ9-THC-mediated elevation in [Ca2+]i occurs independently of [Ca2+]i store depletion. Furthermore, the ROC channel inhibitor, SK&F 96365 was more efficacious at attenuating the Δ9-THC-mediated elevation in [Ca2+]i than SOC channel inhibitors, 2-aminoethoxydiphenyl borate and La3+. Recently, several members of the transient receptor potential canonical (TRPC) channel subfamily have been suggested to operate as SOC or ROC channels. In the present studies, treatment of HPB-ALL cells with 1-oleoyl-2-acetyl-sn-glycerol (OAG), a cell-permeant analog of diacylglycerol (DAG), which gates several members of the TRPC channel subfamily, rapidly elevated [Ca2+]i, as well as prevented a subsequent, additive elevation in [Ca2+]i by Δ9-THC, independent of protein kinase C. Reverse transcriptase-polymerase chain reaction analysis for TRPC1–7 showed that HPB-ALL cells express detectable mRNA levels of only TRPC1. Finally, small interference RNA knockdown of TRPC1 attenuated the Δ9-THC-mediated elevation of [Ca2+]i. Collectively, these results suggest that Δ9-THC-induced elevation in [Ca2+]i is attributable entirely to extracellular calcium influx, which is independent of [Ca2+]i store depletion, and is mediated, at least partially, through the DAG-sensitive TRPC1 channels.
Common methodology is inadequate for studies on the microbicidal activity of neutrophils
Authors: Decleva Eva , Menegazzi Renzo , Busetto Sara , Patriarca Pierluigi , Dri Pietro 
Published: October 2005

Abstract
Microbicidal activity of neutrophils is usually measured by colony-counting techniques after cell lysis in distilled water. While studying the effect of the reduced nicotinamide adenine dinucleotide phosphate-oxidase inhibitor diphenyleneiodonium (DPI) on the staphylocidal activity of neutrophils, we obtained inconsistent results: various degrees of inhibition in some experiments and no effect in others. The lysis step, i.e., dilution of neutrophils in distilled water, was the source of error. Cell-associated microorganisms were not dispersed effectively by this tretment. We overcame this problem by using water at pH 11 for cell lysis. Under these conditions, killing was inhibited completely and reproducibly by DPI. Here, we show that cell lysis in distilled water is incomplete and leads to an overestimate of microbial killing. This hinders identification of partial defects and makes complete defects appear as partial. We found that DPI-treated neutrophils and chronic granulomatous disease neutrophils were completely defective in killing of Staphylococcus aureus and Candida albicans and partially defective in killing of Escherichia coli after lysis with water pH 11, whereas after lysis in distilled water, killing of S. aureus and C. albicans was ∼60% and ∼70% of control killing, respectively, and killing of E. coli was normal. Likewise, killing of S. aureus by myeloperoxidase-deficient neutrophils was severely impaired after lysis in water pH 11 but appeared normal after lysis in distilled water. As most studies about neutrophil microbicidal activity have been performed using distilled water, our findings indicate that previous data about killing defects and the effects of agents that modulate microbicidal activity of neutrophils should be re-evaluated.
Abnormal regulation of the cytoskeletal regulator Rho typifies macrophages of the major murine models of spontaneous autoimmunity
Authors: Fan Hanli , Patel Vimal A , Longacre Angelika , Levine Jerrold S 
Published: October 2005

Abstract
Macrophages (mφ) from prediseased mice of all the major murine models of spontaneous autoimmunity have an identical defect in cytokine expression that is triggered by serum and/or apoptotic cells. We show here that mφ from prediseased mice of the same models of spontaneous autoimmunity share a serum-dependent defect in the activity of Rho, a cytoplasmic G protein and cytoskeletal regulator. Affected strains include those developing lupus (BXSB, LG, MRL/l+, MRL/lpr, NZBWF1) and autoimmune diabetes (nonobese diabetic). No similar defect in Rho activity occurred in seven control strains. In the presence of serum, Rho activity in mφ from all autoimmune-prone strains was reduced to less than 10% of that in control mice. In contrast, under serum-free conditions, Rho activity was ompletely normal in autoimmune-prone mφ. The activities of Ras, another cytoplasmic G protein, and Rac and Cdc42, two additional G protein regulators of the cytoskeleton, were regulated normally in autoimmune-prone strains. Serum-dependent dysregulation of Rho was associated with multiple abnormalities, including increased adhesion to various surfaces, a more spread dendritic morphology, and an altered actin cytoskeletal organization. Our results suggest that mφ from multiple, genetically diverse, autoimmune-prone strains share a mutation or allelic difference affecting signal transduction within a specific Rho-regulatory pathway.
Ceramide catabolism critically controls survival of human dendritic cells
Authors: Franchi Luigi , Malisan Florence , Tomassini Barbara , Testi Roberto 
Published: October 2005

Abstract
The regulation of dendritic cell (DC) survival is crucial for the modulation of adaptive immunity. Ceramide is a lipid mediator of the stress response, which accumulates intracellularly during DC differentiation. We found that ceramide levels are tightly regulated in human DCs and that the pharmacological inhibition of enzymes responsible for ceramide catabolism, such as ceramidases and sphingosine kinases, sensitizes DCs to ceramide-induced cell death. It is important that inhibition of sphingosine kinases, during lipopolysaccharide stimulation, causes extensive ceramide accumulation and death of DCs. These data indicate that ceramide catabolism regulates urvival of human DCs and reveal novel potential targets for the pharmacological manipulation of the immune response.
Neoadjuvant Chemotherapy With High-Dose Ifosfamide, High-Dose Methotrexate, Cisplatin, and Doxorubicin for Patients With Localized Osteosarcoma of the Extremity: A Joint Study by the Italian and Scandinavian Sarcoma Groups
Authors: Ferrari Stefano , Smeland Sigbjorn , Mercuri Mario , Bertoni Franco , Longhi Alessandra , Ruggieri Pietro , Alvegard Thor A. , Picci Piero , Capanna Rodolfo , Bernini Gabriella , Müller Cristoph , Tienghi Amelia , Wiebe Thomas , Comandone Alessandro , Böhling Tom , Del Prever Adalberto Brach , Brosjö Otte , Bacci Gaetano , Sæter Gunnar 
Published: October 2005

Purpose To explore the effect of high-dose ifosfamide in first-line treatment for patients ≤ 40 years of age with nonmetastatic osteosarcoma of the extremity. Patients and Methods From March 1997 to September 2000, 182 patients were evaluated. Primary treatment consisted of two blocks of high-dose ifosfamide (15 g/m2), methotrexate (12 g/m2), cisplatin (120 mg/m2), and doxorubicin (75 mg/m2). Postoperatively, patients received two cycles of doxorubicin (90 mg/m2), and three cycles each of high-dose ifosfamide, methotrexate, and cisplatin (120 to 150 mg/m2). Granulocyte colony-stimulating factor support was mandatory after the high-dose ifosfamide/cisplatin/doxorubicin combination. Results No disease progression was recorded during primary chemotherapy, 164 patients (92%) underwent limb-salvage surgery, four patients (2%) underwent rotation plasty, and 11 patients (6%) had limbs amputated. Three (1.6%) patients died as a result of treatment-related toxicity, and one died as a result of pulmonary embolism after pathologic fracture. Grade 4 neutropenia and thrombocytopenia followed 52% and 31% of all courses, respectively, and mild to severe nephrotoxicity was recorded in 19 patients (10%). The median received dose-intensity compared with protocol was 0.82. With a median follow-up of 55 months, the 5-year probability of event-free survival was 64% (95% CI, 57% to 71%) and overall survival was 77% (95% CI, 67% to 81%), whereas seven patients (4%) experienced local recurrence. Conclusion The addition of high-dose ifosfamide to methotrexate, cisplatin, and doxorubicin in the preoperative phase is feasible, but with major renal and hematologic toxicities, and survival rates similar to those obtained with four-drug regimens using standard-dose ifosfamide. Italian Sarcoma Group/Scandinavian Sarcoma Group study I showed that in a multicenter setting, more than 90% of patients with osteosarcoma of the extremity can undergo conservative surgery.
Multicenter Phase I/II Study of Cetuximab With Paclitaxel and Carboplatin in Untreated Patients With Stage IV Non–Small-Cell Lung Cancer
Authors: Thienelt Christiane D. , Bunn Paul A. , Hanna Nasser , Rosenberg Arthur , Needle Michael N. , Long Michael E. , Gustafson Daniel L. , Kelly Karen 
Published: October 2005

PurposeEpidermal growth factor receptor (EGFR) tyrosine kinase inhibitors have demonstrated antitumor activity in patients with non–small-cell lung cancer (NSCLC). This study examined the safety profile of the monoclonal antibody EGFR inhibitor, cetuximab, when added to paclitaxel and carboplatin in untreated patients with stage IV NSCLC. Secondary objectives included efficacy and paclitaxel and carboplatin pharmacokinetics during cetuximab treatment.Patients and MethodsPatients with tumor evidence of EGFR by immunohistochemistry, performance status of 0 to 2, and measurable disease received paclitaxel 225 mg/m2with carboplatin area under the curve = 6 on day 1 every 3 weeks. Cetuximab was administered at 400 mg/m2, 1 week before paclitaxel and carboplatin, then weekly at 250 mg/m2. The regimen continued until disease progression or intolerable toxicity.ResultsThirty-one of 32 enrolled patients were treated. The most common cetuximab toxicity was rash in 84% of patients (grade 3 in 13%). Pharmacokinetic sampling did not reveal an interaction between carboplatin, paclitaxel, and cetuximab. An objective response was observed in eight patients (26%). With a median follow-up of 19 months, the median time to progression was 5 months, median survival was 11 months, and the 1- and 2-year survival rates were 40% and 16%, respectively.ConclusionThe combination of cetuximab, paclitaxel, and carboplatin was safe and well tolerated in this population of stage IV patients. The response rate, time to progression, and median survival were slightly superior to historical controls treated with paclitaxel and carboplatin alone. A randomized phase II trial has completed accrual.