bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effect of Oxidation on the Platelet-Activating Properties of Low-Density Lipoprotein
Authors: Korporaal Suzanne J.A. , Gorter Gertie , van Rijn Herman J.M. , Akkerman Jan-Willem N. 
Published: February 2005

Objective—Because of the large variation in oxidizing procedures and susceptibility to oxidation of low-density lipoprotein (LDL) and the lack in quantification of LDL oxidation, the role of oxidation in LDL–platelet contact has remained elusive. This study aims to compare platelet activation by native LDL (nLDL) and oxidized LDL (oxLDL).Methods and Results—After isolation, nLDL was dialyzed against FeSO4to obtain LDL oxidized to well-defined extents varying between 0% and >60%. The oxLDL preparations were characterized with respect to their platelet-activating properties. An increase in LDL oxidation enhances platelet activation via 2 independent pathways, 1 signaling via p38MAPKphosphorylation and 1 via Ca2+mobilization. Between 0% and 15% oxidation, the p38MAPKroute enhances fibrinogen binding induced by thrombin receptor (PAR-1)-activating peptide (TRAP), and signaling via Ca2+is absent. At >30% oxidation, p38MAPKsignaling increases further and is accompanied by Ca2+mobilization and platelet aggregation in the absence of a second agonist. Despite the increase in p38MAPKsignaling, synergism with TRAP disappears and oxLDL becomes an inhibitor of fibrinogen binding. Inhibition is accompanied by binding of oxLDL to the scavenger receptor CD36, which is associated with the fibrinogen receptor, αIIbβ3.Conclusion—At >30% oxidation, LDL interferes with ligand binding to integrin αIIbβ3, thereby attenuating platelet functions.
Social Structure and Personality During the Process of Radical Social Change: A Study of Ukraine in Transition
Authors: Paniotto Vladimir , Kohn Melvin , Khmelko Valeriy , Hung HO-Fung 
Published: February 2005

AbstractThis paper investigates the relationships of social structure and personality during a period of radical social change attendant on the early stages of the transformation of Ukraine from socialism to nascent capitalism. It does so by analyzing data secured from face-to-face interviews with a representative sample of urban Ukrainian men and women in 1992-93, together with a follow-up survey three to three and a half years later of all those respondents who at the time of the initial survey either were employed or were seeking paid employment.We found that the over-time correlations – the stabilities – of two underlying dimensions of personality – self-directedness of orientation and a sense of well-being or distress – were startlingly low, by comparison not only to the United States at a time of much greater social stability, but also to Poland at the same time as the Ukrainian study, albeit at a later stage of transition. The stability of a third fundamental dimension of personality – intellectual flexibility – was higher than those of self-directedness of orientation and distress, but considerably lower than past research had led us to expect. Still, despite massive changes in social and economic conditions and great instability of personality, the relationships of social structure with personality were remarkably consistent over time and, with the partial exception of those with the sense of wellbeing or distress, were quite similar to those of both socialist and advanced capitalist societies during times of apparent social stability. Our analyses suggest that consistency in the relationships between social structure and personality despite great change both in social structure and in personality results from the continued stability of proximate conditions of life that link position in the larger social structure to individual personality, and the continued strength of those linkages. Notable among these proximate conditions, for those people who were employed at the times of both the baseline and follow-up surveys, is the substantive complexity of their work.
An Overview
Authors: Milburn Donald T. 
Published: February 2005

• Why does every ultrasound textbook begin with a “physics chapter”? • Don't you know everything you need to know about ultrasound physics? After all, you've probably been performing echocardiograms or sonograms for years. • How will learning more about the physical principles of sound make you a better sonographer? This article will answer these questions in order. You simply cannot be the best if you don't know the physics of sound.
Multifunctional role of Erk5 in multiple myeloma
Authors: Carvajal-Vergara Xonia , Tabera Soraya , Montero Juan C. , Esparís-Ogando Azucena , López-Pérez Ricardo , Mateo Gema , Gutiérrez Norma , Parmo-Cabañas Marisa , Teixidó Joaquín , San Miguel Jesús F. , Pandiella Atanasio 
Published: February 2005

AbstractMultiple myeloma is characterized by the accumulation of terminally differentiated B cells in the bone marrow, due to increased proliferation and restricted apoptosis of the myelomatous clone. Here we have studied the participation of a novel mitogen-activated protein kinase (MAPK) route, the extracellular signal-regulated kinase 5 (Erk5) pathway, in the regulation of myeloma cell proliferation and apoptosis. Erk5 was expressed in cells isolated from patients and in myeloma cell lines. The myeloma growth factor interleukin 6 (IL-6) activated Erk5, and this activation was independent of Ras and Src. Expression of a dominant-negative form of Erk5 restricted the proliferation of myeloma cells and inhibited IL-6–dependent cell duplication. This dominant-negative form also sensitized myeloma cells to the proapoptotic action of dexamethasone and PS341. The latter compound caused a profound decrease in the amount of endogenous Erk5 and was less effective in inducing apoptosis when the level of Erk5 was increased by transfection of Erk5. These results place the Erk5 route as a new regulatory signaling pathway that affects multiple myeloma proliferation and apoptosis.
An anti-CD20–IL-2 immunocytokine is highly efficacious in a SCID mouse model of established human B lymphoma
Authors: Gillies Stephen D. , Lan Yan , Williams Steven , Carr Frank , Forman Stephen , Raubitschek Andrew , Lo Kin-Ming 
Published: February 2005

AbstractWe have engineered an anti-CD20–interleukin 2 (IL-2) immunocytokine (ICK) based on the Leu16 anti-CD20 antibody and have deimmunized both the variable (V) regions as well as the junction between the heavy (H) chain constant region and IL-2. Mutations were made to remove potential T-cell epitopes identified by in silico binding to major histocompatibility complex (MHC) class II molecules. The resulting immunocytokine, DI-Leu16-IL-2, retained full anti-CD20 activity as assessed by fluorescence-activated cell-sorting (FACS) analysis, and had enhanced antibody-dependent cellular cytotoxicity (ADCC) effector function relative to the DI-Leu16 antibody or control anti-CD20 antibody (rituximab). In a severe combined immunodeficient (SCID) mouse model of disseminated, residual lymphoma, anti-CD20–IL-2 immunocytokines based on Leu16 were far more effective at a dose of 0.25 mg/kg than anti-CD20 antibody given at 25/mg/kg, despite a shorter half-life of the ICK. Anti-CD20–IL-2 was also far more effective than a control ICK targeted to an antigen with greatly reduced expression on Daudi tumor cells, or various combinations of anti-CD20 antibodies and IL-2. Antitumor activity of DI-Leu16-IL-2 was shown to partially but not entirely depend on Fc receptor (R) binding, suggesting that ADCC and targeting of IL-2 both play roles in the mechanism of tumor clearance. Based on these animal models, DI-Leu16-IL-2 could offer therapeutic potential for patients with CD20 positive lymphoma. Clinical trials are currently under development.
Induction of tumor NK-cell immunity by anti-CD69 antibody therapy
Authors: Esplugues Enric , Vega-Ramos Javier , Cartoixà David , Vazquez Berta N. , Salaet Ignasi , Engel Pablo , Lauzurica Pilar 
Published: February 2005

AbstractThe leukocyte activation marker CD69 is a novel regulator of the immune response, modulating the production of cytokines including transforming growth factor-β (TGF-β). We have generated an antimurine CD69 monoclonal antibody (mAb), CD69.2.2, which down-regulates CD69 expression in vivo but does not deplete CD69-expressing cells. Therapeutic administration of CD69.2.2 to wild-type mice induces significant natural killer (NK) cell–dependent antitumor responses to major histocompatibility complex (MHC) class I low RMA-S lymphomas and to RM-1 prostatic carcinoma lung metastases. These in vivo antitumor responses are comparable to those seen in CD69-/- mice. Enhanced host NK cytotoxic activity correlates with a reduction in NK-cell TGF-β production and is independent of tumor priming. In vitro studies demonstrate the novel ability of anti-CD69 mAbs to activate resting NK cells in an Fc receptor–independent manner, resulting in a substantial increase in both NK-cell cytolytic activity and interferon γ (IFNγ) production. Modulation of the innate immune system with monoclonal antibodies to host CD69 thus provides a novel means to antagonize tumor growth and metastasis.
Plasma membrane sequestration of apoptotic protease-activating factor-1 in human B-lymphoma cells: a novel mechanism of chemoresistance
Authors: Sun Yu , Orrenius Sten , Pervaiz Shazib , Fadeel Bengt 
Published: February 2005

Abstract
Burkitt lymphoma (BL) is a highly aggressive B-cell neoplasm harboring chromosomal rearrangements of the c-myc oncogene. BL cells frequently resist apoptosis induction by chemotherapeutic agents; however, the mechanism of unresponsiveness has not been elucidated. Here, we show that cytochrome c fails to stimulate apoptosome formation and caspase activation in cytosolic extracts of human BL-derived cell lines, due to insufficient levels of apoptotic protease-activating factor-1 (Apaf-1). Enforced expression of Apaf-1 increased its concentration in the cytosolic compartment, restored cytochrome c-dependent caspase activation, and rendered the prototypic Raji BL cell line sensitive to etoposide- and staurosporine-induced apoptosis. Surprisingly, in nontransfected BL cells, the bulk of Apaf-1 was found to associate with discrete domains in the plasma membrane. Disruption of lipid raft domains or the actin cytoskeleton of Raji cells liberated Apaf-1 and restored sensitivity to cytochrome c–dependent apoptosis, indicating that constitutive Apaf-1 retained its ability to promote caspase activation. Moreover, disruption of lipid rafts sensitized BL cells to apoptosis induced by etoposide. Together, our findings suggest that ectopic (noncytosolic) localization of Apaf-1 may constitute a novel mechanism of chemoresistance in B lymphoma.
Graft-versus-tumor response in patients with multiple myeloma is associated with antibody response to BCMA, a plasma-cell membrane receptor
Authors: Bellucci Roberto , Alyea Edwin P. , Chiaretti Sabina , Wu Catherine J. , Zorn Emmanuel , Weller Edie , Wu Bingyan , Canning Christine , Schlossman Robert , Munshi Nikhil C. , Anderson Kenneth C. , Ritz Jerome 
Published: February 2005

AbstractDonor lymphocyte infusions (DLIs) induce effective graft-versus-tumor responses in patients with multiple myeloma who relapse after allogeneic hematopoietic stem-cell transplantation. The graft-versus-myeloma response is presumably mediated primarily by donor T cells, but recent studies have also demonstrated the presence of antibodies specific for a variety of myeloma-associated antigens in patients who achieve complete remission after DLI. One of the B-cell antigens identified in these studies was B-cell maturation antigen (BCMA), a transmembrane receptor of the tumor necrosis factor (TNF) superfamily that is selectively expressed by mature B cells. The present studies were undertaken to characterize the functional significance of antibodies to BCMA in vivo. Using transfected cells expressing BCMA, antibodies in patient serum were found to react with the cell-surface domain of BCMA. Post-DLI patient serum was able to induce complement-mediated lysis and antibody-dependent cellular cytotoxicity (ADCC) of transfected cells and primary myeloma cells expressing BCMA. BCMA antibodies were only found in post-DLI responders and not in other allogeneic transplant patients or healthy donors. These results demonstrate that BCMA is a target of donor B-cell immunity in patients with myeloma who respond to DLI. Antibody responses to cell-surface BCMA may contribute directly to tumor rejection in vivo.
DNA repeat arrays in chicken and human genomes and the adaptive evolution of avian genome size
Authors: Hughes Austin L , Piontkivska Helen 
Published: February 2005

Abstract
Background
Birds have smaller average genome sizes than other tetrapod classes, and it has been proposed that a relatively low frequency of repeating DNA is one factor in reduction of avian genome sizes.

Results
DNA repeat arrays in the sequenced portion of the chicken (Gallus gallus) autosomes were quantified and compared with those in human autosomes. In the chicken 10.3% of the genome was occupied by DNA repeats, in contrast to 44.9% in human. In the chicken, the percentage of a chromosome occupied by repeats was positively correlated with chromosome length, but even the largest chicken chromosomes had repeat densities much lower than those in human, indicating that avoidance of repeats in the chicken is not confined to minichromosomes. When 294 simple sequence repeat types shared between chicken and human genomes were compared, mean repeat array length and maximum repeat array length were significantly lower in the chicken than in human.

Conclusions
The fact that the chicken simple sequence repeat arrays were consistently smaller than arrays of the same type in human is evidence that the reduction in repeat array length in the chicken has involved numerous independent evolutionary events. This implies that reduction of DNA repeats in birds is the result of adaptive evolution. Reduction of DNA repeats on minichromosomes may be an adaptation to permit chiasma formation and alignment of small chromosomes. However, the fact that repeat array lengths are consistently reduced on the largest chicken chromosomes supports the hypothesis that other selective factors are at work, presumably related to the reduction of cell size and consequent advantages for the energetic demands of flight.
Narrative Exposure Therapy as a treatment for child war survivors with posttraumatic stress disorder: Two case reports and a pilot study in an African refugee settlement
Authors: Onyut Lamaro P , Neuner Frank , Schauer Elisabeth , Ertl Verena , Odenwald Michael , Schauer Maggie , Elbert Thomas 
Published: February 2005

Abstract
Background
Little data exists on the effectiveness of psychological interventions for children with posttraumatic stress disorder (PTSD) that has resulted from exposure to war or conflict-related violence, especially in non-industrialized countries. We created and evaluated the efficacy of KIDNET, a child-friendly version of Narrative Exposure Therapy (NET), as a short-term treatment for children.

Methods
Six Somali children suffering from PTSD aged 12–17 years resident in a refugee settlement in Uganda were treated with four to six individual sessions of KIDNET by expert clinicians. Symptoms of PTSD and depression were assessed pre-treatment, post-treatment and at nine months follow-up using the CIDI Sections K and E.

Results
Important symptom reduction was evident immediately after treatment and treatment outcomes were sustained at the 9-month follow-up. All patients completed therapy, reported functioning gains and could be helped to reconstruct their traumatic experiences into a narrative with the use of illustrative material.

Conclusions
NET may be safe and effective to treat children with war related PTSD in the setting of refugee settlements in developing countries.
Effect of urbanization on bone mineral density: A Thai epidemiological study
Authors: Pongchaiyakul Chatlert , Nguyen Tuan V , Kosulwat Vongsvat , Rojroongwasinkul Nipa , Charoenkiatkul Somsri , Rajatanavin Rajata 
Published: February 2005

Abstract
Background
The incidence of fractures in rural populations is lower than in urban populations, although the reason for this difference is unclear. This cross-sectional study was designed to examine the difference in bone mineral density (BMD), a primary predictor of fracture risk, between urban and rural Thai populations.

Methods
Femoral neck and lumbar spine BMD was measured by dual-energy X-ray absorptiometry (GE Lunar, Madison, WI) in 411 urban and 436 rural subjects (340 men and 507 women), aged between 20 and 84 years. Body mass index (BMI) was calculated from weight and height.

Results
After adjusting for age and body weight in an analysis of covariance model, femoral neck BMD in rural men and women was significantly higher than those in urban men and women (P < 0.001), but the difference was not observed at the lumbar spine. After stratifying by sex, age group, and BMI category, the urban-rural difference in femoral neck BMD became more pronounced in men and women aged <50 years and with BMI ≥ 25 kg/m2.

Conclusions
These data suggest that femoral neck BMD in rural men and women was higher than their counterparts in urban areas. This difference could potentially explain part of the urban-rural difference in fracture incidence.
Differential effects of ERK and p38 signaling in BMP-2 stimulated hypertrophy of cultured chick sternal chondrocytes
Authors: Reilly Gwendolen C , Golden Eleanor B , Grasso-Knight Giovi , Leboy Phoebe S 
Published: February 2005

Abstract
Background
During endochondral bone formation, the hypertrophy of chondrocytes is accompanied by selective expression of several genes including type X collagen and alkaline phosphatase. This expression is stimulated by inducers including BMPs and ascorbate. A 316 base pair region of the type X collagen (Col X) promoter has been previously characterized as the site required for BMP regulation. The intent of this study was to examine the role of Mitogen Activated Protein (MAP) and related kinase pathways in the regulation of Col X transcription and alkaline phosphatase activity in pre-hypertrophic chick chondrocytes.

Results
Using a luciferase reporter regulated by the BMP-responsive region of the type X collagen promoter, we show that promoter activity is increased by inhibition of extra-cellular signal regulated kinases 1 or 2 (ERK1/2). In contrast the ability of BMP-2 to induce alkaline phosphatase activity is little affected by ERK1/2 inhibition. The previously demonstrated stimulatory affect of p38 on Col X was shown to act specifically at the BMP responsive region of the promoter. The inhibitory effect of the ERK1/2 pathway and stimulatory effect of the p38 pathway on the Col X promoter were confirmed by the use of mutant kinases. Inhibition of upstream kinases: protein kinase C (PKC) and phosphatidylinositol 3-(PI3) kinase pathways increased basal Col X activity but had no effect on the BMP-2 induced increase. In contrast, ascorbate had no effect on the BMP-2 responsive region of the Col X promoter nor did it alter the increase in promoter activity induced by ERK1/2 inhibition. The previously shown increase in alkaline phosphatase activity induced by ascorbate was not affected by any kinase inhibitors examined. However some reduction in the alkaline phosphatase activity induced by the combination of BMP-2 and ascorbate was observed with ERK1/2 inhibition.

Conclusion
Our results demonstrate that ERK1/2 plays a negative role while p38 plays a positive role in the BMP-2 activated transcription of type X collagen. This regulation occurs specifically at the BMP-2 responsive promoter region of Col X. Ascorbate does not modulate Col X at this region indicating that BMP-2 and ascorbate exert their action on chondrocyte hypertrophy via different transcriptional pathways. MAP kinases seem to have only a modest effect on alkaline phosphatase when activity is induced by the combination of both BMP-2 and ascorbate.
In vitro and in vivo evaluation of NCX 4040 cytotoxic activity in human colon cancer cell lines
Authors: Tesei Anna , Ulivi Paola , Fabbri Francesco , Rosetti Marco , Leonetti Carlo , Scarsella Marco , Zupi Gabriella , Amadori Dino , Bolla Manlio , Zoli Wainer 
Published: February 2005

Abstract
Background
Nitric oxide-releasing nonsteroidal antiinflammatory drugs (NO-NSAIDs) are reported to be safer than NSAIDs because of their lower gastric toxicity. We compared the effect of a novel NO-releasing derivate, NCX 4040, with that of aspirin and its denitrated analog, NCX 4042, in in vitro and in vivo human colon cancer models and investigated the mechanisms of action underlying its antitumor activity.

Methods
In vitro cytotoxicity was evaluated on a panel of colon cancer lines (LoVo, LoVo Dx, WiDr and LRWZ) by sulforhodamine B assay. Cell cycle perturbations and apoptosis were evaluated by flow cytometry. Protein expression was detected by Western blot. In the in vivo experiments, tumor-bearing mice were treated with NCX 4040, five times a week, for six consecutive weeks.

Results
In the in vitro studies, aspirin and NCX 4042 did not induce an effect on any of the cell lines, whereas NCX 4040 produced a marked cytostatic dose-related effect, indicating a pivotal role of the -NO2 group. Furthermore, in LoVo and LRWZ cell lines, we observed caspase-9 and -3-mediated apoptosis, whereas no apoptotic effect was observed after drug exposure in WiDr or LoVo Dx cell lines. In in vivo studies, both NCX 4040 and its parental compound were administered per os. NCX 4040 induced a 40% reduction in tumor weight. Conversely, aspirin did not influence tumor growth at all.

Conclusions
NCX 4040, but not its parental compound, aspirin, showed an in vitro and in vivo antiproliferative activity, indicating its potential usefulness to treat colon cancer.
HIV-1 Tat protein enhances Microtubule polymerization
Authors: de Mareuil Jean , Carre Manon , Barbier Pascale , Campbell Grant R , Lancelot Sophie , Opi Sandrine , Esquieu Didier , Watkins Jennifer D , Prevot Charles , Braguer Diane , Peyrot Vincent , Loret Erwann P 
Published: February 2005

Abstract
Background
HIV infection and progression to AIDS is characterized by the depletion of T cells, which could be due, in part, to apoptosis mediated by the extra-cellular HIV-encoded Tat protein as a consequence of Tat binding to tubulin. Microtubules are tubulin polymers that are essential for cell structure and division. Molecules that target microtubules induce apoptosis and are potent anti-cancer drugs. We studied the effect on tubulin polymerization of three Tat variants: Tat HxB2 and Tat Eli from patients who are rapid progressors (RP) and Tat Oyi from highly exposed but persistently seronegative (HEPS) patients. We compared the effect on tubulin polymerization of these Tat variants and peptides corresponding to different parts of the Tat sequence, with paclitaxel, an anti-cancer drug that targets microtubules.

Results
We show that Tat, and specifically, residues 38–72, directly enhance tubulin polymerization. We demonstrate that Tat could also directly trigger the mitochondrial pathway to induce T cell apoptosis, as shown in vitro by the release of cytochrome c from isolated mitochondria.

Conclusions
These results show that Tat directly acts on microtubule polymerization and provide insights into the mechanism of T cell apoptosis mediated by extra-cellular Tat.