bluuebunny/crossref_metadata_2025_split huggingface dataset:
A Temporal Dissociation of Subliminal versus Supraliminal Fear Perception: An Event-related Potential Study
Authors: Liddell Belinda J. , Williams Leanne M. , Rathjen Jennifer , Shevrin Howard , Gordon Evian 
Published: March 2004

Abstract
Current theories of emotion suggest that threat-related stimuli are first processed via an automatically engaged neural mechanism, which occurs outside conscious awareness. This mechanism operates in conjunction with a slower and more comprehensive process that allows a detailed evaluation of the potentially harmful stimulus (LeDoux, 1998). We drew on the Halgren and Marinkovic (1995) model to examine these processes using event-related potentials (ERPs) within a backward masking paradigm. Stimuli used were faces with fear and neutral (as baseline control) expressions, presented above (supraliminal) and below (subliminal) the threshold for conscious detection. ERP data revealed a double dissociation for the supraliminal versus subliminal perception of fear. In the subliminal condition, responses to the perception of fear stimuli were enhanced relative to neutral for the N2 “excitatory” component, which is thought to represent orienting and automatic aspects of face processing. By contrast, supraliminal perception of fear was associated with relatively enhanced responses for the late P3 “inhibitory” component, implicated in the integration of emotional processes. These findings provide evidence in support of Halgren and Marinkovic's temporal model of emotion processing, and indicate that the neural mechanisms for appraising signals of threat may be initiated, not only automatically, but also without the need for conscious detection of these signals.
Insulin-like growth factor binding protein-3 antagonizes the effects of retinoids in myeloid leukemia cells
Authors: Ikezoe Takayuki , Tanosaki Sakae , Krug Utz , Liu Bingrong , Cohen Pinchas , Taguchi Hirokuni , Koeffler H. Phillip 
Published: March 2004

Abstract
Insulin-like growth factor binding protein-3 (IGFBP-3) can cause growth suppressive and proapoptotic effects on retinoids in many types of cancer cells. However, the expression and effects of IGFBP-3 in myeloid leukemia cells have not been elucidated. In this study, we found no IGFBP-3 expression in the human myeloid leukemia cell lines either at baseline or after stimulation with all-trans retinoic acid (ATRA). Human recombinant IGFBP-3 induced growth arrest and apoptosis of HL-60 and NB4 cells. We have previously identified RXRα as a nuclear receptor for IGFBP-3 and have proceeded to examine further the role of this interaction in leukemia cell lines. In signaling assays, IGFBP-3 potently suppressed RAR- and VDR-mediated signaling while enhancing RXR signaling. Interestingly, when IGFBP-3 was administered to these cells in combination with an RAR-selective ligand, the ability of these retinoids to induce differentiation was blunted. On the other hand, IGFBP-3 enhanced the effect of an RXR-selective ligand to induce differentiation of HL-60 and NB4 cells. Further studies showed that IGFBP-3 down-regulated (at the transcriptional level) the retinoid-induced expression of C/EBPϵ in NB4 cells. Taken together, these results indicate that IGFBP-3 has antiproliferative activity against myeloid leukemia cells; while it enhances signaling through RXR/RXR, it blunts signaling by activated RAR/RXR.
Artificial antigen-presenting constructs efficiently stimulate minor histocompatibility antigen–specific cytotoxic T lymphocytes
Authors: Oosten Liesbeth E. M. , Blokland Els , van Halteren Astrid G. S. , Curtsinger Julie , Mescher Matthew F. , Falkenburg J. H. Frederik , Mutis Tuna , Goulmy Els 
Published: March 2004

AbstractCytotoxic T lymphocytes (CTLs) specific for hematopoietic-restricted minor histocompatibility antigens (mHags) are important reagents for adoptive immunotherapy of relapsed leukemia after allogeneic stem cell transplantation. However, expansion of these CTLs to therapeutic numbers is often hampered by the limited supply of antigen-presenting cells (APCs). Therefore, we evaluated whether cell-sized latex beads coated with HLA/mHag complexes HLA-A2/HA-1 or HLA-A2/HA-2 and recombinant CD80 and CD54 molecules can replace professional APCs. The artificial antigen-presenting constructs (aAPCs) effectively stimulated HA-1– and HA-2–specific CTL clones as shown by ligand-specific expansion, cytokine production, and maintenance of cytotoxic activity, without alteration of CTL phenotype. Furthermore, HA-1–specific polyclonal CTL lines were enriched as efficiently by aAPCs as by autologous HA-1 peptide-pulsed dendritic cells. Thus, aAPCs coated with HLA/mHag complexes, CD80, and CD54 may serve as tools for in vitro enrichment of immunotherapeutic mHag-specific CTL lines.
Treatment with arsenic trioxide (ATO) and MEK1 inhibitor activates the p73-p53AIP1 apoptotic pathway in leukemia cells
Authors: Lunghi Paolo , Costanzo Antonio , Levrero Massimo , Bonati Antonio 
Published: March 2004

Abstract
Arsenic trioxide (ATO) induces differentiation and apoptosis of malignant cells in vitro and in vivo and has been used in the treatment of a variety of hematologic malignancies. We found that in NB4 acute promyelocytic and in K562 erythroleukemia cell lines treatment with the MEK1 inhibitors PD98059 and PD184352 greatly enhances apoptotic cell death induced by ATO alone. Combined treatment results in the induction of the p53AIP1 (p53-regulated apoptosis-inducing protein 1) gene in both cell lines. Because NB4 and K562 cell lines carry an inactive p53, we investigated the possible role of p73, a p53 paralogue that has been shown to regulate several p53 target genes including p21, Bax, and p53AIP1. We found that MEK1 inhibitors reduce the levels of dominant-negative (ΔN) p73 proteins and promote the accumulation of endogenous p73α through its transcriptional activation and its tyrosine phosphorylation, resulting in p21 up-regulation and significant inhibition of cell growth. ATO reduces ΔNp73 levels and promotes a p300-mediated acetylation of endogenous p73, thus favoring cell cycle arrest and apoptosis. Finally, the combined treatment with MEK1 inhibitors and ATO enhances the affinity of phosphoacetylated p73 for the p53AIP1 promoter in vivo, as determined by chromatin immunoprecipitation experiments, leading to p53AIP1 up-regulation and increased apoptosis. (Blood. 2004; 104:519-525)
Blood mononuclear cell gene expression profiles characterize the oxidant, hemolytic, and inflammatory stress of sickle cell disease
Authors: Jison Maria L. , Munson Peter J. , Barb Jennifer J. , Suffredini Anthony F. , Talwar Shefali , Logun Carolea , Raghavachari Nalini , Beigel John H. , Shelhamer James H. , Danner Robert L. , Gladwin Mark T. 
Published: March 2004

Abstract
In sickle cell disease, deoxygenation of intra-erythrocytic hemoglobin S leads to hemoglobin polymerization, erythrocyte rigidity, hemolysis, and microvascular occlusion. Ischemia-reperfusion injury, plasma hemoglobin-mediated nitric oxide consumption, and free radical generation activate systemic inflammatory responses. To characterize the role of circulating leukocytes in sickle cell pathogenesis we performed global transcriptional analysis of blood mononuclear cells from 27 patients in steady-state sickle cell disease (10 patients treated and 17 patients untreated with hydroxyurea) compared with 13 control subjects. We used gender-specific gene expression to validate human microarray experiments. Patients with sickle cell disease demonstrated differential gene expression of 112 genes involved in heme metabolism, cell-cycle regulation, antioxidant and stress responses, inflammation, and angiogenesis. Inducible heme oxygenase-1 and downstream proteins biliverdin reductase and p21, a cyclin-dependent kinase, were up-regulated, potentially contributing to phenotypic heterogeneity and absence of atherosclerosis in patients with sickle cell disease despite endothelial dysfunction and vascular inflammation. Hydroxyurea therapy did not significantly affect leukocyte gene expression, suggesting that such therapy has limited direct anti-inflammatory activity beyond leukoreduction. Global transcriptional analysis of circulating leukocytes highlights the intense oxidant and inflammatory nature of steady-state sickle cell disease and provides insight into the broad compensatory responses to vascular injury.
Altered leukocyte response to CXCL12 in patients with warts hypogammaglobulinemia, infections, myelokathexis (WHIM) syndrome
Authors: Gulino Anna Virginia , Moratto Daniele , Sozzani Silvano , Cavadini Patrizia , Otero Karel , Tassone Laura , Imberti Luisa , Pirovano Silvia , Notarangelo Lucia D. , Soresina Roberta , Mazzolari Evelina , Nelson David L. , Notarangelo Luigi D. , Badolato Raffaele 
Published: March 2004

AbstractThe chemokine receptor CXCR4 and its functional ligand, CXCL12, are essential regulators of development and homeostasis of hematopoietic and lymphoid organs. Heterozygous truncating mutations in the CXCR4 intracellular tail cause a rare genetic disease known as WHIM syndrome (warts, hypogammaglobulinemia, infections, myelokathexis), whose pathophysiology remains unclear. We report CXCR4 function in 3 patients with WHIM syndrome carrying heterozygous truncating mutations of CXCR4. We show that CXCR4 gene mutations in WHIM patients do not affect cell surface expression of the chemokine receptor and its internalization upon stimulation with CXCL12. Moreover, no significant differences in calcium mobilization in response to CXCL12 are found. However, the chemotactic response of both polymorphonuclear cells and T lymphocytes in response to CXCL12 is increased. Furthermore, immunophenotypic analysis of circulating T and B lymphocytes reveals a decreased number of memory B cells and of naive T cells and an accumulation of effector memory T cells associated with a restricted T-cell repertoire. Based on our results, we suggest that the altered leukocyte response to CXCL12 may account for the pathologic retention of mature polymorphonuclear cells in the bone marrow (myelokathexis) and for an altered lymphocyte trafficking, which may cause the immunophenotyping abnormalities observed in WHIM patients. (Blood. 2004;104:444-452)
The contribution of inherited and acquired thrombophilic defects, alone or combined with antiphospholipid antibodies, to venous and arterial thromboembolism in patients with systemic lupus erythematosus
Authors: Brouwer Jan-Leendert P. , Bijl Marc , Veeger Nic J. G. M. , Kluin-Nelemans Hanneke C. , van der Meer Jan 
Published: March 2004

Abstract
Systemic lupus erythematosus (SLE) is associated with an increased risk of venous (VTE) and arterial thromboembolism (ATE). Lupus anticoagulant (LA) and anticardiolipin antibodies (ACAs) are established risk factors. We assessed the contribution of deficiencies of antithrombin, protein C, total protein S, factor V Leiden, the prothrombin G20210A mutation and APC resistance, either alone or in various combinations with LA and/or ACAs, to the thrombotic risk in a cohort of 144 consecutive patients with SLE. Median follow-up was 12.7 years. VTE had occurred in 10% and ATE in 11% of patients. LA,ACAs, factor V Leiden, and the prothrombin mutation were identified as risk factors for VTE. Annual incidences of VTE were 2.01 (0.74-4.37) in patients with one of these disorders and 3.05 (0.63-8.93) in patients with 2 disorders. The risk of VTE was 20- and 30-fold higher, respectively, compared with the normal population. In contrast with LA and ACAs, thrombophilic disorders did not influence the risk of ATE. In conclusion, factor V Leiden and the prothrombin mutation contribute to the risk of VTE in patients with SLE, and potentiate this risk when one of these thrombophilic defects are combined with LA and/or ACAs.
Effects of inflammatory cytokines on the release and cleavage of the endothelial cell–derived ultralarge von Willebrand factor multimers under flow
Authors: Bernardo Aubrey , Ball Chalmette , Nolasco Leticia , Moake Joel F. , Dong Jing-fei 
Published: March 2004

AbstractADAMTS13 cleaves ultralarge and hyperreactive von Willebrand factor (ULVWF) freshly released from activated endothelial cells to smaller and less active forms. This process may be affected by the amount of ULVWF released and the processing capacity of ADAMTS13, contributing to the development of thrombotic diseases. We examined the effects of inflammatory cytokines on the release and cleavage of ULVWF to evaluate potential links between inflammation and thrombosis. Human umbilical vein endothelial cells were treated with interleukin 6 (IL-6), IL-8, or tumor necrosis factor α (TNF-α), and the formation of platelet-decorated ULVWF strings was quantitated. IL-8 and TNF-α significantly stimulated the release of ULVWF in a dose-dependent manner. IL-6 induced ULVWF release only when it was in complex with the soluble IL-6 receptor. IL-6, but not IL-8 nor TNF-α, inhibited the cleavage of ULVWF strings by ADAMTS13 under flowing, but not static, conditions. These results suggest that inflammatory cytokines may stimulate the ULVWF release (IL-8 and TNF-α) and inhibit the ULVWF cleavage (IL-6), resulting in the accumulation of hyperreactive ULVWF in plasma and on the surface of endothelial cells to induce platelet aggregation and adhesion on the vascular endothelium. The findings describe a potential linkage between inflammation and thrombosis that may be of therapeutic importance.
In vitro–expanded human CD4+CD25+ T-regulatory cells can markedly inhibit allogeneic dendritic cell–stimulated MLR cultures
Authors: Godfrey Wayne R. , Ge Ying G. , Spoden Darrin J. , Levine Bruce L. , June Carl H. , Blazar Bruce R. , Porter Stephen B. 
Published: March 2004

AbstractCD4+CD25+ T-regulatory (Treg) cells have been shown to critically regulate self- and allograft tolerance in several model systems. Studies of human Treg cells have been restricted by the small number present in peripheral blood and their naturally hypoproliferative state. To better characterize Treg suppressor cell function, we determined methods for the isolation and expansion of these cells. Stringent magnetic microbead-based purification was required for potent suppressor cell line generation. Culture stimulation with cell-sized Dynabeads coated with anti-CD3 and anti-CD28 monoclonal antibodies, CD4+ feeder cells, and interleukin 2, provided for marked expansion in cell number (100-fold), with retention and enhancement of suppressor function. The potent Treg cell lines suppressed proliferation in dendritic cell-driven allo-mixed lymphocyte reaction (MLR) cultures by more than 90%. The Treg-derived suppressor cells functioned early in allo-MLR because expression of activation antigens and accumulation of cytokines was nearly completely prevented. Importantly, cultured Treg cells also suppressed activated and matured dendritic cell-driven responses. These results demonstrate that short-term suppressor cell lines can be generated, and they can express a very potent suppressive activity. This approach will enable more detailed biologic studies of Treg cells and facilitate the evaluation of cultured Treg cells as a novel form of immunosuppressive therapy. (Blood. 2004;104:453-461)
Antigen-induced regulatory T cells
Authors: Vigouroux Stephane , Yvon Eric , Biagi Ettore , Brenner Malcolm K. 
Published: March 2004

AbstractRegulatory T cells participate in immunologic homeostasis by active suppression of inappropriate immune responses. Regulatory T lymphocytes expressing CD4 and CD25 antigens and naturally present in the peripheral blood were the first to be phenotypically characterized. However, their small number and antigen nonspecific suppression has prompted efforts to identify and dissect antigen-specific regulatory T cells. In this review we discuss how antigen-specific regulatory T cells can be identified, the cellular and molecular mechanisms underlying their induction and activity, and the challenges facing their potential clinical application.
Does the Type II Glucocorticoid Receptor Mediate Cortisol-Induced Suppression in Pituitary Responsiveness to Gonadotropin-Releasing Hormone?
Authors: Breen Kellie M. , Stackpole Catherine A. , Clarke Iain J. , Pytiak Andrew V. , Tilbrook Alan J. , Wagenmaker Elizabeth R. , Young Elizabeth A. , Karsch Fred J. 
Published: March 2004

Abstract
Stress-like elevations in plasma cortisol suppress LH pulse amplitude in ovariectomized ewes by inhibiting pituitary responsiveness to GnRH. Here we sought to identify the receptor mediating this effect. In a preliminary experiment GnRH and LH pulses were monitored in ovariectomized ewes treated with cortisol plus spironolactone, which antagonizes the type I mineralocorticoid receptor (MR), or with cortisol plus RU486, which antagonizes both the type II glucocorticoid receptor (GR) and the progesterone receptor (PR). Cortisol alone reduced LH pulse amplitude, but not pulsatile GnRH secretion, indicating that it reduced pituitary responsiveness to endogenous GnRH. RU486, but not spironolactone, reversed this suppression. We next tested whether RU486 reverses the inhibitory effect of cortisol on pituitary responsiveness to exogenous GnRH pulses of fixed amplitude, frequency, and duration. Hourly GnRH pulses were delivered to ovariectomized ewes in which endogenous GnRH pulses were blocked by estradiol during seasonal anestrus. Cortisol alone reduced the amplitude of LH pulses driven by the exogenous GnRH pulses. RU486, but not an antagonist of PR (Organon 31710), prevented this suppression. Thus, the efficacy of RU486 in blocking the suppressive effect of cortisol is attributed to antagonism of GR, not PR. Together, these observations imply that the type II GR mediates cortisolinduced suppression of pituitary responsiveness to GnRH.
Methanol Electrooxidation on Carbon-Supported Pt3Ru2Sn Ternary Catalyst
Authors: Kim Taeyoon , Takahashi Masashi , Nagai Masayuki , Kobayashi Koichi 
Published: March 2004

Abstract
The electrocatalytic methanol oxidation over Pt–Ru–Sn/C ternary alloy catalysts was investigated. The catalytic activity of Pt3Ru2Sn/C was significantly higher than that of PtRu/C. Sn in ternary alloy catalyst modified the Pt electronic structure without the large increase of Pt–Pt bond distance, which may enhance the catalytic activity for methanol oxidation by improving CO tolerance.
Inadequate Prevention of NSAID-Induced Gastrointestinal Events
Authors: Herings Ron MC , Goettsch Wim G 
Published: March 2004

BACKGROUND Use of nonsteroidal antiinflammatory drugs (NSAIDs) is a well-known cause of gastrointestinal (GI) adverse events. To protect patients at risk, several strategies are advised, including concomitant treatment with proton-pump inhibitors or switching to cyclooxygenase (COX)-2 selective NSAIDs. It is as yet unknown how many patients at risk for NSAID-induced events are protected. OBJECTIVE To estimate the number of patients using GI preventive treatment while at risk for NSAID-induced GI events. METHODS Records of patients using NSAIDs consecutively for at least 100 days (from 2001 to 2002) were obtained from the PHARMO system in the Netherlands (N = 1 000 000). GI preventive treatments were classified as adequate or inadequate based on evidence-based criteria. Adequate treatment was defined as concomitant use of misoprostol (>400 μg daily), histamine2-antagonists (≥2 times recommended dose) or proton-pump inhibitors (≥1 recommended dose), or alternative treatment with COX-2 selective inhibitors. RESULTS A total of 10 121 patients met the study inclusion criteria; 70% were women. One or more preventive strategies were prescribed in 4340 patients (42.9%), of which 2799 (64.5%) were adequate and 1541 (35.5%) inadequate. Prescribing of adequate preventive treatments increased with the number of risk factors, from 13.3% among those with no additional risk factors to 61.9% for those with ≥4 risk factors. CONCLUSIONS Although risk factors for GI damage were recognized, a large number of patients in the Netherlands were not or were inadequately protected against potential NSAID-associated GI damage. Despite recommendations, and even in the presence of ≥4 risk factors, almost 40% of these patients were not prescribed adequate GI preventive treatment.
Glycosylated Hemoglobin, Cardiovascular, and Renal Outcomes in a Pharmacist-Managed Clinic
Authors: Cioffi Seth T , Caron Michael F , Kalus James S , Hill Patricia , Buckley Thomas E 
Published: March 2004

BACKGROUND Pharmacists' responsibilities in caring for patients with diabetes mellitus are expanding. However, few data are available to support pharmacists optimizing therapy and improving outcomes in these patients. OBJECTIVE To determine the effect of a clinical pharmacist—directed diabetes management clinic on glycemic control and cardiovascular and renal parameters in patients with type 2 diabetes. METHODS A nonrandomized, prospective study was conducted in 70 Veterans Affairs patients. Patients met with the pharmacist every 6–8 weeks for approximately 30 minutes for education, medication counseling, monitoring, and management. The primary endpoint was the impact of 9–12 months of participation in the clinic on glycosylated hemoglobin (HbA1C). Secondarily, we evaluated body weight, total cholesterol, low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol, triglycerides, systolic and diastolic blood pressure, and level of microalbuminuria. All comparisons were made using a paired t-test at a significance level of p ≤ 0.05. RESULTS HbA1C significantly decreased from 10.3% ± 2.2% at baseline to 6.9% ± 1.1% (mean ± SD) during the 9- to 12-month evaluation period (p < 0.001). The secondary endpoints including systolic (p < 0.001) and diastolic (p < 0.001) blood pressure, total cholesterol (p < 0.001), LDL-C (p < 0.001), triglycerides (p = 0.006), and level of microalbuminuria (p < 0.001) also were reduced at 9–12 months. CONCLUSIONS This study demonstrated that a clinical pharmacist can effectively care for patients with diabetes referred by their primary care provider because of poor glycemic control.
Implementation and Evaluation of Cultural Competency Training for Pharmacy Students
Authors: Assemi Mitra , Cullander Chris , Hudmon Karen Suchanek 
Published: March 2004

BACKGROUND The demographic composition of the US population is rapidly changing. As a result, pharmacists increasingly face the need to interact effectively with and provide care for patients whose ethnic or cultural background may differ from their own. While schools implement curricula to provide pharmacy students with cultural awareness, knowledge, and communication skills they will need in practice, few assessment tools exist to evaluate the impact or effectiveness of such training. OBJECTIVE To implement and assess the impact of a cultural competency training course designed specifically for pharmacy students. METHODS An 8-hour elective course offering basic cultural competency training was provided to 60 first- through fourth-year pharmacy students in 2003. A 12-item survey assessing students' perceived awareness, knowledge, and communication skills in the areas of cultural competence and cross-cultural communication skills was administered immediately prior to and upon completion of the course. Surveys were linked, enabling estimation of within-student change as a result of exposure to the program. RESULTS Fifty-six paired surveys (96.6% of participants) were analyzable. Responses to all survey items (p < 0.05) and total scores (t55 = 16.27; p < 0.001) increased significantly from pre- to posttraining. The mean ± SD 12-item pretraining scale score was 33.35 ± 5.48 (range 21–44), and the mean posttraining scale score was 47.88 ± 4.90 (range 36–59). CONCLUSIONS Survey results suggest that the course successfully raised student awareness of diversity and provided basic knowledge and skills pertaining to cultural competence and cross-cultural communication.