bluuebunny/crossref_metadata_2025_split huggingface dataset:
TNF-related apoptosis-inducing ligand is involved in neutropenia of systemic lupus erythematosus
Authors: Matsuyama Wataru , Yamamoto Masuki , Higashimoto Ikkou , Oonakahara Ken-ichi , Watanabe Masaki , Machida Kentarou , Yoshimura Teizo , Eiraku Nobutaka , Kawabata Masaharu , Osame Mitsuhiro , Arimura Kimiyoshi 
Published: March 2004

AbstractNeutropenia is a common laboratory finding in systemic lupus erythematosus (SLE). However, the molecular mechanism of SLE neutropenia has not been fully explained. In this study, we examined whether TNF-related apoptosis-inducing ligand (TRAIL) is involved in the pathogenesis of SLE neutropenia using samples from SLE patients. Serum TRAIL levels in SLE patients with neutropenia were significantly higher than those of SLE patients without neutropenia and healthy volunteers. Serum TRAIL levels showed a significant negative correlation with neutrophil counts in SLE patients. The expression of TRAIL receptor 3 was significantly lower in SLE patients with neutropenia than in patients without neutropenia or in healthy volunteers. Treatment with glucocorticoids negated the decrease of TRAIL receptor 3 expression on neutrophils of SLE patients. TRAIL may accelerate neutrophil apoptosis of neutrophils from SLE patients, and autologous T cells of SLE patients, which express TRAIL on surface, may kill autologous neutrophils. Interferon gamma and glucocorticoid modulated the expression of TRAIL on T cells of SLE patients and also modulated the expression of cellular Fas-associating protein with death domain–like interleukin-1β–converting enzyme (FLICE)–inhibitory protein (cFLIP), an inhibitor of death receptor signaling, in neutrophils. Thus, our results provide a novel insight into the molecular pathogenesis of SLE neutropenia.
Human marrow stromal cells activate monocytes to secrete osteopontin, which down-regulates Notch1 gene expression in CD34+ cells
Authors: Iwata Mineo , Awaya Norihiro , Graf Lynn , Kahl Christoph , Torok-Storb Beverly 
Published: March 2004

AbstractThe hematopoietic microenvironment, approximated in vitro by long-term marrow cultures (LTCs), consists of both nonhematopoietic-derived stromal elements and hematopoietic-derived monocyte/macrophages. To better understand the consequences of monocyte-stroma interactions, we compared gene expression profiles of CD14+ peripheral blood monocytes and HS-27a stromal cells cultured alone and together in cocultures. Results from 7 separate experiments revealed 22 genes were significantly up- or down-regulated in the cocultures, with osteopontin (OPN) up-regulated more than 15-fold. The microarray OPN data were confirmed by Northern blot, real-time polymerase chain reaction (PCR), and by detection of OPN protein. High levels of OPN gene expression were also detected in 2- to 3-week-old primary LTCs. Using Transwells we determined that stromal cells were secreting a factor that up-regulated OPN gene expression in CD14+ cells. When CD34+ cells were cultured in the presence of purified OPN, tyrosine phosphorylation of a 34-kDa molecule was increased 2- to 3-fold, an effect that was diminished in the presence of an OPN neutralizing monoclonal antibody. In addition, Notch1 gene expression was decreased 5-fold in OPN-treated CD34+ cells. We conclude that interactions between stroma and monocytes can result in activities that limit the role of Notch signaling in hematopoietic regulation. (Blood. 2004;103:4496-4502)
Actin cytoskeleton-dependent down-regulation of early IgE-mediated signaling in human basophils
Authors: Vilariño Natalia , MacGlashan Donald W 
Published: March 2004

AbstractTwo regions of down-regulation of FcɛRI [high-affinity immunogloublin E (IgE) receptor] signaling have been localized recently in basophils. An early down-regulatory step is located proximal to syk and appears responsible for a transient syk phosphorylation in antigen-stimulated basophils. A second, more distal region appears responsible for the transient activation of the ras–extracellular-regulated kinase (Erk) pathway when syk phosphorylation is sustained in anti-IgE-stimulated basophils. As the actin cytoskeleton has been demonstrated to inhibit the early FcɛRI signaling in rat basophilic leukemia cells, we explored the hypothesis that the actin cytoskeleton was responsible for the transience of syk phosphorylation in antigen-stimulated basophils. The inhibition of F-actin polymerization with latrunculin A induced a sustained syk phosphorylation in basophils stimulated with an optimal dose of the antigen benzyl penicilloyl–human serum albumin. However, in the presence of latrunculin A, Erk phosphorylation remained transient after stimulation with the antigen or anti-IgE. Latrunculin A also increased downstream events such as histaminerelease, leukotriene C4 release, and the intracellular calcium signal, although some of these effects were not specific for an immunologic stimulus. Our results suggest that the actin cytoskeleton is responsible for down-regulation of FcɛRI signaling at a point located proximal to syk phosphorylation. Moreover, the fact that latrunculin A did not result in sustained Erk phosphorylation supports the presence of a second down-regulatory step between syk and Erk that cannot be overcome by a sustained early signal.
Synergistic induction of CXCL9 and CXCL11 by Toll-like receptor ligands and interferon-γ in fibroblasts correlates with elevated levels of CXCR3 ligands in septic arthritis synovial fluids
Authors: Proost Paul , Verpoest Sara , Van De Borne Kirsten , Schutyser Evemie , Struyf Sofie , Put Willy , Ronsse Isabelle , Grillet Bernard , Opdenakker Ghislain , Van Damme Jo 
Published: March 2004

AbstractThe synovial cavity constitutes the ideal stage to study the interplay between microbial Toll-like receptor (TLR) ligands and cytokines. Infiltrated leukocytes and synovial fibroblasts produce cytokine- and chemokine-induced proteases for remodeling the extracellular matrix. The regulation of chemokine function for attraction and activation of leukocytes constitutes a key feature in host immunity and resolution of inflammation after infection. Enhanced levels of the CXC chemokine ligand (CXCL9)/monokine induced by interferon-γ (IFN-γ) and CXCL11/IFN-inducible T cell α chemoattractant, two chemoattractants for activated T cells and natural killer cells, and ligands for CXC chemokine receptor 3 (CXCR3) were detected in the synovial fluid of septic arthritis compared with osteo- and crystal arthritis patients. In vitro, IFN-γ and TLR3 ligation by double-stranded RNA (dsRNA) induced the expression of CXCL9 and CXCL11 in leukocytes and skin-muscle fibroblasts, whereas ligation of TLR2, TLR4, TLR5, and TLR9 by peptidoglycan (PGN), lipopolysaccharide (LPS), flagellin, and unmethylated CpG oligonucleotides, respectively, did not. PGN and LPS, but not unmethylated CpG oligonucleotides, even inhibited IFN-γ-induced CXCL9 and CXCL11 expression in leukocytes. In sharp contrast, in fibroblasts, the TLR ligands PGN, dsRNA, LPS, and flagellin synergized with IFN-γ for the production of CXCL9 and CXCL11. Although TLR ligands stimulate leukocytes to produce CXCL8/interleukin-8 during the early innate defense, they contribute less to the production of CXCR3 ligands, whereas fibroblasts are important sources of CXCR3 ligands. These results illustrate the complex interaction between cytokines and TLR ligands in infection.
The generation of T cell memory: a review describing the molecular and cellular events following OX40 (CD134) engagement
Authors: Weinberg Andrew D , Evans Dean E , Thalhofer Colin , Shi Tom , Prell Rodney A 
Published: March 2004

AbstractOX40 (CD134), a membrane-bound member of the tumor necrosis factor-receptor superfamily, is expressed primarily on activated CD4+ T cells. Following engagement on the cell surface, OX40 delivers a costimulatory signal that leads to potent, proinflammatory effects. Engagement of OX40 during antigen (Ag)-specific stimulation of T cells leads to increased production of memory T cells, increased migration of Ag-specific T cells, enhanced cytokine production by effector T cells, and the ability to break peripheral T cell tolerance in vivo. Therefore, OX40 engagement in vivo could have important ramifications for the enhancement of vaccine strategies and inhibition of unwanted inflammation. This review summarizes the molecular and cellular events that occur following OX40 engagement during Ag-specific T cell activation.
A randomized controlled trial of aromatherapy massage in a hospice setting
Authors: Soden Katie , Vincent Karen , Craske Stephen , Lucas Caroline , Ashley Sue 
Published: March 2004

Research suggests that patients with cancer, particularly in the palliative care setting, are increasingly using aromatherapy and massage. There is good evidence that these therapies may be helpful for anxiety reduction for short periods, but few studies have looked at the longer term effects. This study was designed to compare the effects of four-week courses of aromatherapy massage and massage alone on physical and psychological symptoms in patients with advanced cancer. Forty-two patients were randomly allocated to receive weekly massages with lavender essential oil and an inert carrier oil (aromatherapy group), an inert carrier oil only (massage group) or no intervention. Outcome measures included a Visual Analogue Scale (VAS) of pain intensity, the Verran and Snyder-Halpern (VSH) sleep scale, the Hospital Anxiety and Depression (HAD) scale and the Rotterdam Symptom Checklist (RSCL). We were unable to demonstrate any significant long-term benefits of aromatherapy or massage in terms of improving pain control, anxiety or quality of life. However, sleep scores improved significantly in both the massage and the combined massage (aromatherapy and massage) groups. There were also statistically significant reductions in depression scores in the massage group. In this study of patients with advanced cancer, the addition of lavender essential oil did not appear to increase the beneficial effects of massage. Our results do suggest, however, that patients with high levels of psychological distress respond best to these therapies.
The Value of Routine Serum Carcino-Embryonic Antigen Measurement and Computed Tomography in the Surveillance of Patients After Adjuvant Chemotherapy for Colorectal Cancer
Authors: Chau Ian , Allen Mark J. , Cunningham David , Norman Andrew R. , Brown Gina , Ford Hugo E.R. , Tebbutt Niall , Tait Diana , Hill Mark , Ross Paul J. , Oates Jacqui 
Published: March 2004

Purpose This analysis aims to evaluate routine carcino-embryonic antigen (CEA) and computed tomography (CT) of thorax, abdomen, and pelvis as part of protocol-specified follow-up policy for colorectal cancer (CRC). Patients and Methods Patients with resected stage II and III CRC were randomly assigned to bolus fluorouracil/leucovorin or protracted venous infusion fluorouracil. Following completion of chemotherapy, patients were seen in clinic at regular intervals for 5 years. CEA was measured at each clinic visit, and CT of thorax, abdomen, and pelvis was performed at 12 and 24 months after commencement of chemotherapy. Results Between 1993 and 1999, 530 patients were recruited. The median follow-up was 5.6 years. Disease relapses were observed in 154 patients. Relapses were detected by symptoms (n = 65), CEA (n = 45), CT (n = 49), and others (n = 9). Fourteen patients, whose relapses were detected by CT, had a concomitant elevation of CEA and were included in both groups. The CT-detected group had a better survival compared with the symptomatic group from the time of relapse (P = .0046). Thirty-three patients (21%) proceeded to potentially curative surgery for relapse and enjoyed a better survival than those who did not (P < .00001). For patients who underwent hepatic or pulmonary metastatic resection, 13 (26.5%) were in the CT group, eight (17.8%) in the CEA group, and only two (3.1%) in the symptomatic group (CT v symptomatic, P < .001; CEA v symptomatic, P = .015). Conclusion Surveillance CT and CEA are valuable components of postoperative follow-up in stage II and III colorectal cancer.
Efficacy of Topotecan and Cyclophosphamide Given in a Phase II Window Trial in Children With Newly Diagnosed Metastatic Rhabdomyosarcoma: A Children’s Oncology Group Study
Authors: Walterhouse David O. , Lyden Elizabeth R. , Breitfeld Philip P. , Qualman Stephen J. , Wharam Moody D. , Meyer William H. 
Published: March 2004

Purpose To determine the antitumor activity and toxicity of topotecan given immediately after cyclophosphamide as window therapy, then in combination with conventional agents in pediatric patients with newly diagnosed metastatic rhabdomyosarcoma (RMS). Patients and Methods Sixty-one patients younger than 21 years with newly diagnosed metastatic RMS or undifferentiated sarcoma were assigned window therapy (weeks 0 to 6) with topotecan (0.75 mg/m2 daily × 5 every 21 days) immediately after cyclophosphamide (250 mg/m2 daily × 5 every 21 days; TC). We continued to give these agents in combination with vincristine (VTC) to patients who showed objective improvement, partial response (PR), or complete response (CR) to TC and alternated courses of VTC with vincristine, dactinomycin and cyclophosphamide (VAC) during weeks 6 to 41 (VTC/VAC). Those who showed no response or progressive disease after TC received only VAC. All patients received radiotherapy to sites of unresected disease (weeks 15 to 21). Results The overall response rate (CR + PR) to TC was 47% (95% CI, 35% to 60%). Tumor size ≤ 5 cm was associated with early response. Myelosuppression was the primary toxicity to TC. Overall 3-year disease-free survival and survival were estimated to be 10% (95% CI, 2% to 19%) and 20% (95% CI, 8% to 32%), respectively. Toxicity profiles for patients who received VTC/VAC or VAC alone were comparable. Conclusion Topotecan after cyclophosphamide is a combination that is active against newly diagnosed RMS, with an acceptable toxicity profile. Disease-free survival and overall survival, however, remain disappointing for children with metastatic RMS at diagnosis.
Genetic Variants in the UDP-glucuronosyltransferase 1A1 Gene Predict the Risk of Severe Neutropenia of Irinotecan
Authors: Innocenti Federico , Undevia Samir D. , Iyer Lalitha , Xian Chen Pei , Das Soma , Kocherginsky Masha , Karrison Theodore , Janisch Linda , Ramírez Jacqueline , Rudin Charles M. , Vokes Everett E. , Ratain Mark J. 
Published: March 2004

Purpose Severe toxicity is commonly observed in cancer patients receiving irinotecan. UDP-glucuronosyltransferase 1A1 (UGT1A1) catalyzes the glucuronidation of the active metabolite SN-38. This study prospectively evaluated the association between the prevalence of severe toxicity and UGT1A1 genetic variation. Patients and Methods Sixty-six cancer patients with advanced disease refractory to other treatments received irinotecan 350 mg/m2 every 3 weeks. Toxicity and pharmacokinetic data were measured during cycle 1. UGT1A1 variants (−3279G>T, −3156G>A, promoter TA indel, 211G>A, 686C>A) were genotyped. Results The prevalence of grade 4 neutropenia was 9.5%. Grade 4 neutropenia was much more common in patients with the TA indel 7/7 genotype (3 of 6 patients; 50%) compared with 6/7 (3 of 24 patients; 12.5%) and 6/6 (0 of 29 patients; 0%) (P = .001). The TA indel genotype was significantly associated with the absolute neutrophil count nadir (7/7 < 6/7 < 6/6, P = .02). The relative risk of grade 4 neutropenia was 9.3 (95% CI, 2.4 to 36.4) for the 7/7 patients versus the rest of the patients. Pretreatment total bilirubin levels (mean ± standard deviation) were significantly higher in patients with grade 4 neutropenia (0.83 ± 0.08 mg/dL) compared to those without grade 4 neutropenia (0.47 ± 0.03 mg/dL; P < .001). The −3156G>A variant seemed to distinguish different phenotypes of total bilirubin within the TA indel genotypes. The −3156 genotype and the SN-38 area under the concentration versus time curve were significant predictors of ln(absolute neutrophil count nadir; r2 = 0.51). Conclusion UGT1A1 genotype and total bilirubin levels are strongly associated with severe neutropenia, and could be used to identify cancer patients predisposed to the severe toxicity of irinotecan. The hypothesis that the −3156G>A variant is a better predictor of UGT1A1 status than the previously reported TA indel requires further testing.
Activation of the Hexosamine Pathway Leads to Phosphorylation of Insulin Receptor Substrate-1 on Ser307 and Ser612 and Impairs the Phosphatidylinositol 3-Kinase/Akt/Mammalian Target of Rapamycin Insulin Biosynthetic Pathway in RIN Pancreatic β-Cells
Authors: Andreozzi Francesco , D’Alessandris Cristina , Federici Massimo , Laratta Emanuela , Del Guerra Silvia , Del Prato Stefano , Marchetti Piero , Lauro Renato , Perticone Francesco , Sesti Giorgio 
Published: March 2004

AbstractMany adverse effects of glucose were attributed to its increased routing through the hexosamine pathway (HBP). There is evidence for an autocrine role of the insulin signaling in β-cell function. We tested the hypothesis that activation of the HBP induces defects in insulin biosynthesis by affecting the insulin-mediated protein translation signaling. Exposure of human pancreatic islets and RIN β-cells to glucosamine resulted in reduction in glucose- and insulin-stimulated insulin biosynthesis, which in RIN β-cells was associated with impairment in insulin-stimulated insulin receptor substrate-1 (IRS-1) phosphorylation at Tyr608 and Tyr628, which are essential for engaging phosphatidylinositol 3-kinase (PI 3-kinase). These changes were accompanied by impaired activation of PI 3-kinase, and activation of Akt/mammalian target of rapamycin/phosphorylated heat- and acid-stable protein-1/p70S6 kinase pathway. RIN β-cells exposed to high glucose exhibited increased c-Jun N-terminal kinase (JNK) and ERK1/2 activity, which was associated with increased IRS-1 phosphorylation at serine (Ser)307 and Ser612, respectively, that inhibits coupling of IRS-1 to the insulin receptor and is upstream of the inhibition of IRS-1 tyrosine phosphorylation. Azaserine reverted the stimulatory effects of high glucose on JNK and ERK1/2 activity and IRS-1 phosphorylation at Ser307 and Ser612. Glucosamine mimicked the stimulatory effects of high glucose on JNK and ERK1/2 activity and IRS-1 phosphorylation at Ser307 and Ser612. Inhibition of JNK and MAPK kinase-1 activity reverted the negative effects of glucosamine on insulin-mediated protein synthesis. These results suggest that activation of the HBP accounts, in part, for glucose-induced phosphorylation at Ser307 and Ser612 of IRS-1 mediated by JNK and ERK1/2, respectively. These changes result in impaired coupling of IRS-1 and PI 3-kinase, and activation of the Akt/mammalian target of rapamycin/phosphorylated heat- and acid-stable protein-1/p70S6 kinase pathway.
Chemical defense of an opilionid (Acanthopachylus aculeatus)
Authors: Eisner Thomas , Rossini Carmen , González Andrés , Eisner Maria 
Published: March 2004

SUMMARY
The opilionid Acanthopachylus aculeatus was shown to produce a defensive secretion containing quinones (2,3-dimethyl-1,4-benzoquinone,2,5-dimethyl-1,4-benzoquinone and 2,3,5-trimethyl-1,4-benzoquinone),confirming the findings reported nearly a half century ago in a classic study. The mechanism by which the opilionid puts the secretion to use is described. When disturbed, the animal regurgitates enteric fluid, which it conveys by intercoxal clefts to the anterolateral corners of the carapace, where the two gland openings are situated. It then injects some of its quinonoid secretion into the fluid, and conveys the mixed liquid along the length of its flanks by way of two special channels. Such a discharge mechanism may be widespread among opilionids of the family Gonyleptidae (suborder Laniatores), to which A. aculeatus belongs. In a bioassay based on a scratch reflex in decapitated cockroaches (Periplaneta americana) the liquid effluent of A. aculeatus was shown to be potently irritating. Use of the effluent was demonstrated to protect the opilionid against ants (Formica exsectoides). Wolf spiders (Lycosa ceratiola) were shown to be minimally affected by the effluent (they showed little response when the fluid was added to their mouthparts as they fed on mealworms, their normal laboratory prey), although they proved to be aversive to mere contact with the opiliond itself, and to reject the animal without inducing it to discharge. A. aculeatus may therefore contain distasteful factors besides its glandular products.
Mitochondria-rich cell activity in the yolk-sac membrane of tilapia(Oreochromis mossambicus) larvae acclimatized to different ambient chloride levels
Authors: Lin Li-Yih , Hwang Pung-Pung 
Published: March 2004

SUMMARY
Mitochondria-rich cells (MRCs) in the yolk-sac membrane of tilapia(Oreochromis mossambicus) larvae were examined by Na+/K+-ATPase immunocytochemistry and vital staining for glycoproteins following acclimation to high (7.5–7.9 mmol l–1), normal (0.48–0.52 mmol l–1) or low (0.002–0.007 mmol l–1) ambient Cl–levels. With a combination of concanavalin-A (Con-A)–Texas-Red conjugate staining (larvae exposed to the dye in vivo in the water) and a monoclonal antibody raised against Na+/K+-ATPase, MRCs were easily recognized and presumed to be active when Con-A-positive (i.e. with their apical membrane in contact with the water) or inactive when Con-A-negative. The proportion of active cells gradually increased during a 48-h acclimation to low-Cl– medium but decreased during acclimation to high-Cl– medium. Total densities of MRCs did not change when ambient chloride levels were altered. Furthermore, in live larvae exposed to changes in ambient Cl–, yolk-sac MRCs,vitally stained with DASPEI and subsequently traced in time, did not significantly alter turnover. The polymorphism of the apical membrane compartment of the MRCs represents structural modification of the active MRCs. Yolk-sac pavement cells labeled with the membrane marker FM1-43 (fluorescent lipophilic tracer) were shown to cover active MRCs in larvae transferred from normal to high ambient Cl– levels, thereby inactivating the MRCs.
Metabolism of the sub-Antarctic caterpillar Pringleophaga marioni during cooling, freezing and thawing
Authors: Sinclair Brent J. , Klok C. Jaco , Chown Steven L. 
Published: March 2004

SUMMARY
Although general models of the processes involved in insect survival of freezing exist, there have been few studies directly investigating physiological processes during cooling, freezing and thawing, without which these models remain hypothetical. Here, we use open-flow respirometry to investigate the metabolism of the freeze-tolerant sub-Antarctic caterpillar Pringleophaga marioni Viette (Lepidoptera: Tineidae) during cooling,freezing and thawing and to compare animals exposed to non-lethal(–5.8°C) and lethal (–6.0°C, after which caterpillars are moribund for several days, and –18°C, after which caterpillars are completely unresponsive) freezing stress. We found a large decrease in metabolic rate (that is not associated with freezing) at–0.6±0.1°C and calculated a Q10 of 2.14×103 at this breakpoint. This breakpoint is coincident with the critical thermal minimum (CTmin) and is hypothesised to be a metabolic manifestation of the latter, possibly a failure of the Na+/K+-ATPase pump. This provides a plausible link between processes at the cellular level and observations of the action of the CTmin at tissue and whole-organism levels. Caterpillars froze at –4.6±0.1°C and had detectable metabolism when frozen. Post-thaw, metabolic rates were lower than pre-freezing measurements. Post-thaw metabolic rates did not differ between temperatures that did and did not kill the caterpillars, which suggests that mortality may be a result of a breakdown in processes at the organismal,rather than cellular, level of organisation.