bluuebunny/crossref_metadata_2025_split huggingface dataset:
Statins as novel immunomodulators: From cell to potential clinical benefit
Authors: Mach François 
Published: September 2003

SummaryIn the last decades, substantial progress has been made in understanding the relationship between lipid disorders and prevention of cardiac ischemic disease. Statins competitively inhibit 3-hydroxyl-3-methylglutaryl coenzyme A (HMG-CoA) reductase, an enzyme crucial to cholesterol biosynthesis. Statins have long been thought to exert their benefits by reducing cholesterol synthesis, but the fact that mevalonate is the precursor of isoprenoids that regulate diverse cellular functions has led investigators to examine pleiotropic effects for these agents. Statins have never been shown to be involved in the immune response, although two clinical trials have suggested that in heart transplant patients, statin therapy has beneficial effects on the incidence of cardiac rejection, coronary vasculopathy, and survival.Major Histocompatibility Complex class II (MHC-II) molecules, which affect the immune response and organ rejection after transplantation, may be induced by the pro-inflammatory cyto-kine interferon gamma (IFN-γ). Recently, it has been demonstrated that statins repress the induction of MHC-II by IFN-γ in vitro, and thus may suggest a potential role for statins as immunosuppressive agents in vivo. Indeed, two recent in vivo studies performed on different animal models provide further evidence that statin-treatment positively influence immunological disorders.This publication was partially financed by Serono Foundation for the Advancement of Medical Science.Part of this paper was originally presented at the 2nd International Workshop on New Therapeutic Targets in Vascular Biology from February 6-9, 2003 in Geneva, Switzerland.
Platelet-leukocyte aggregation under shear stress: Differential involvement of selectins and integrins
Authors: Hu Hu , Varon David , Hjemdahl Paul , Savion Naphtali , Schulman Sam , Li Nailin 
Published: September 2003

SummaryPlatelets and leukocytes can form heterotypic aggregates. We studied how shear stress influences platelet-leukocyte aggregation (PLA). Shear stress was applied to hirudinized blood, using a cone-and-plate(let) analyzer. Platelet and leukocyte activation and PLA formation were monitored by flow cytometry. Shear stress per se increased platelet P-selectin expression, leukocyte CD11b expression, and PLA formation. Shear-induced hetero-typic aggregation was seen among monocytes and neutrophils, but not lymphocytes. ADP induced marked PLA formation, but this was reduced by shear stress. fMLP mildly increased PLA formation, and this effect was enhanced by shear stress. P-selec-tin blockade abolished, whilst GPIIb/IIIa blockade enhanced shear- and agonist-induced PLA formation. At 1800 s-1, shear-and agonist-induced PLA formation were maintained or further enhanced with GPIIb/IIIa blockade alone, but reduced by simultaneous blockade of GPIIb/IIIa, CD11b, and CD18. In conclusion, shear stress per se enhances PLA formation. With agonist stimulation, shear stress enhances PLA formation primarily mediated by integrins, but attenuates PLA formation primarily mediated by P-selectin. The present results indicate that P-selectin-mediated bridging is essential for the initiation of PLA formation, while integrin-bridgings contribute importantly to the stability of heterotypic conjugates under high shear stress.
Restricted BV gene usage by factor VIII-reactive CD4+ T cells in inhibitor-positive patients with severe hemophilia A
Authors: Bayry Jagadeesh , Pashov Anastas , Kaveri Srini , d’Oiron Roseline , Stieltjes Natalie , Roussel-Robert Valeri , Kazatchkine Michel , Boyer Olivier , Lacroix-Desmazes Sébastien , Misra Namita 
Published: September 2003

SummaryIn the present study, we have analyzed the T cell receptor (TCR) repertoires of CD4+ T cells isolated from peripheral blood of 10 inhibitor-positive patients with severe hemophilia A. The distribution of complementarity determining region (CDR3) lengths of the beta chain of the TCRs was analyzed by spectratyping prior to and following in vitrostimulation of the cells with human factor VIII (FVIII). The repertoires of CD4+ T cells of patients were perturbed when compared to those of healthy blood donors. The perturbations of T cell repertoires were heterogeneous among patients with respect to the number and the nature of V-beta (BV) families that exhibited expansion following incubation with FVIII. Some patients showed alterations in one or two BV families, others exhibited more perturbed repertoires affecting 5 to 8 of the 14 BV families tested. Alterations of BV2, BV5 and/or BV9 were consistently found after incubation of CD4+ T cells in the presence of FVIII in 80% of the patients. These findings indicate that the presence of FVIII inhibitors in patients with severe hemophilia A is associated with measurable perturbations of the CD4+ T cell repertoire that results from oligoclonal expansion of FVIII-specific cells and may be relevant for the design of strategies aimed at modulating the anti-FVIII immune responses by T cell-targeted therapy
Essential Role of Junctional Adhesion Molecule-1 in Basic Fibroblast Growth Factor–Induced Endothelial Cell Migration
Authors: Naik Meghna U. , Vuppalanchi Deepika , Naik Ulhas P. 
Published: September 2003

Objective—Recently, we have shown that blocking of junctional adhesion molecule-1/A (JAM-1/A) inhibits basic fibroblast growth factor (bFGF)-induced angiogenesis. Because the process of endothelial cell proliferation is a key initial step of neovascularization, we studied the effect of functional knockdown of JAM-1 on human umbilical vein endothelial cell (HUVEC) adhesion and migration induced by bFGF.Methods and Results—We introduced small interfering RNAs specific to JAM-1 in HUVECs, stimulated them with bFGF, and studied the resultant adhesion and migration of these cells on vitronectin and fibronectin. We show that depletion of JAM-1 inhibits bFGF-induced HUVEC migration specifically on vitronectin. This inhibition is not attributable to the failure of junctional organization, because expression and distribution of other junctional proteins remained unaffected. This inhibition was in fact attributed to an inability of JAM-1–depleted HUVECs to adhere and spread on vitronectin. Furthermore, we find that JAM-1–depleted HUVECs failed to activate extracellular signal–related kinase (ERK) in response to bFGF treatment.Conclusions—Our results show that JAM-1 is required for the bFGF-induced ERK activation that leads to endothelial cell migration on vitronectin. These data thus implicate JAM-1 as an integral part of both bFGF and ERK signaling pathways in endothelial cells.
Cyclosporin A Enhances Interleukin-8 Expression by Inducing Activator Protein-1 in Human Aortic Smooth Muscle Cells
Authors: Murakami Ryuichiro , Kambe Fukushi , Mitsuyama Hirohito , Okumura Kenji , Murohara Toyoaki , Niwata Satoru , Yamamoto Ryohei , Seo Hisao 
Published: September 2003

Objective—Cyclosporin A (CsA) and tacrolimus (FK506) are widely used as immunosuppressants. However, their use has been hampered by various adverse effects, such as acceleration of atherosclerosis. Interleukin (IL)-8, a chemotactic cytokine, plays an important role in pathogenesis of atherosclerosis. We thus investigated whether synthesis of IL-8 from primary human aortic smooth muscle cells is influenced by CsA and FK506.Methods and Results—Northern blot analysis revealed that CsA increased IL-8 mRNA level and enhanced its increase by epidermal growth factor or tumor necrosis factor-α. In contrast, FK506 had no effect on the mRNA level. IL-8 accumulation in culture media was also increased by CsA. Stability of IL-8 mRNA was not affected by CsA, whereas luciferase reporter gene assay using the human IL-8 promoter revealed that CsA significantly augmented the promoter activity. Electrophoretic mobility shift assay showed that binding activity of activator protein (AP)-1 was increased by CsA, and introduction of a mutation into the AP-1 site in the promoter abolished its CsA-dependent activation. The increased AP-1 binding activity was accompanied by c-Fos synthesis.Conclusions—CsA stimulates synthesis of IL-8 via activation of AP-1 in human aortic smooth muscle cells, providing a novel aspect of biological effects of CsA on the cells.
Pioglitazone Inhibits LOX-1 Expression in Human Coronary Artery Endothelial Cells by Reducing Intracellular Superoxide Radical Generation
Authors: Mehta Jawahar L. , Hu Bo , Chen Jiawei , Li Dayuan 
Published: September 2003

Objective—LOX-1, a novel lectin-like receptor for oxidized LDL (ox-LDL), is expressed in response to ox-LDL, angiotensin II (Ang II), tumor necrosis factor (TNF)-α, and other stress stimuli. It is highly expressed in atherosclerotic tissues. Peroxisome proliferator–activated receptor (PPAR)-γ ligands, such as pioglitazone, exert antiatherosclerotic effects. This study examined the regulation of LOX-1 expression in human coronary artery endothelial cells (HCAECs) by pioglitazone.Methods and Results—Fourth generation HCAECs were treated with ox-LDL, Ang II, or TNF-α with or without pioglitazone pretreatment. All 3 stimuli upregulated LOX-1 expression (mRNA and protein). Pioglitazone, in a concentration-dependent manner, reduced LOX-1 expression (P<0.01 versus ox-LDL, Ang II, or TNF-α alone). Ox-LDL, Ang II, and TNF-α each enhanced intracellular superoxide radical generation, and pioglitazone pretreatment reduced superoxide generation (P<0.01 versus ox-LDL, Ang II, or TNF-α). Furthermore, all 3 stimuli upregulated the expression of the transcription factors nuclear factor-κB and activator protein-1 (determined by electrophoretic mobility shift assay), and pioglitazone pretreatment reduced this expression (P<0.01 versus ox-LDL, Ang II, or TNF-α). To determine the biological significance of pioglitazone-mediated downregulation of LOX-1, we studied monocyte adhesion to ox-LDL–treated HCAECs. Pioglitazone reduced the adhesion of monocytes to activated HCAECs in a fashion similar to that produced by antisense to LOX-1 mRNA.Conclusions—These observations suggest that the PPAR-γ ligand pioglitazone reduces intracellular superoxide radical generation and subsequently reduces the expression of transcription factors, expression of the LOX-1 gene, and monocyte adhesion to activated endothelium. The salutary effect of PPAR-γ ligands in atherogenesis may involve the inhibition of LOX-1 and the adhesion of monocytes to endothelium.
From Oral Practice to Written Record in Ramesside Deir el-Medina
Authors: Haring Ben 
Published: September 2003

AbstractThe thousands of hieratic ostraca and papyri from the Ramesside settlement of necropolis workmen at Deir el-Medina include many texts about private business and legal matters. The majority of standard formulas in these records did not develop before the first half of the 20th dynasty, whereas most of the formulas current in administrative texts of the necropolis already existed in the 19th dynasty. The later increase in and formalization of private and legal texts suggest that writing became only gradually popular in village life. Studies of similar processes in anthropological and historical literature help to explain this development in an exceptionally literate village community. Parmi les milliers des ostraca et des papyrus hiératiques du village des ouvriers de la nécropole de Deir el-Medina, de l'époque ramesside, on trouve un grand nombre de textes relatifs aux affaires privées et juridiques. La plupart de ces textes comprennent des formules standardisées datant de la première moitié de la 20ième dynastie, tandis que la majorité des formules habituelles dans les textes administratifs de la nécropole existaient déjà plus tôt. L'accroissement et la formalisation tardifs des textes privés et juridiques suggère que l'écriture ne se répandait que lentement dans le village. Les études de procès similaires dans la littérature anthropologique et historique nous aident à expliquer ce dévéloppement dans une communauté exceptionellement lettrée.
The Jewish Merchants in the Light of Eleventh-Century Geniza Documents
Authors: Gil Moshe 
Published: September 2003

AbstractThis article deals with various aspects of trade in the 11th century as attested by documents written by Jewish merchants, or regarding them, found in the Cairo Geniza. The following topics are discussed: (a) Partnership; it seems that all transactions were carried out by way of partnership, each party acting in a different locality, and dealing with imports and exports from one country to the other. (b) The methods of accounting, based on regular reports between partners. (c) The ways of marketing the goods. (d) The payments, and matters of credit, price reductions, etc. (e) Disputes between merchants, and the ways of settling them, an oath being the most conclusive argument. (f) The nature and functions of a kind of leader of the merchants, wakīl al-tujjār. Cet article traite de différents aspects du commerce au 11ème siècle, tels qu'ils sont attestés dans les documents écrits par des marchands juifs, ou dans des documents qui les concernent, préservés dans la Geniza du Caire. Les points principaux en sont : (a) L'association; il semble que toutes les transactions s'effectuaient par l'intermédiaire d'associés, chacun des associés agissant dans une localité différente et pratiquant en commerce d'importations et d'exportations d'un pays à l'autre. (b) Les systèmes de comptabilité qui étaient fondés sur des comptes-rendus réguliers échangés entre les associés. (c) Les méthodes de vente. (d) Les modes de payement, de crédit, les réductions de prix, etc. (e) Les conflits entre les marchands et les actions entreprises pour les résoudre. (f) Les fonctions du wakīl al-tujjār, le "chef des marchands".
Colonial Misunderstanding of an Efficient Peasant Institution: Land Settlement and Mushā Tenure in Mandate Palestine, 1921-47
Authors: Nadan Amos 
Published: September 2003

AbstractThe accepted wisdom is that the mushā in Palestine was an archaic system that blocked any chance of development, since no one had any inducement to improve his land. But this study of the mushā, as part of a set of institutions, contradicts that wisdom. The mushā in Palestine was an efficient, dynamic economic institution that facilitated investment. There was no need for land reform, which only proved destructive to the economy of the fallāhīn. It nullified the advantages inherent in the system and, unexpectedly, facilitated the transfer of lands from Arabs to Jews. La vision généralement admise est que le mushā en Palestine était un système archaïque qui faisait obstacle à toute perspective de développement, puisque personne n'était incité à améliorer sa terre. Mais notre étude du mushā contredit cette vision. Le mushā en Palestine était une institution économique efficace et dynamique qui facilitait l'investissement. La réforme foncière qui abolit le mushā a été destructrice pour l'économie des fallāhīn. La réforme a annulé les avantages inhérents au système et, de façon inattendue, a facilité le transfert de terres des Arabes aux Juifs.
On Cultural Conceptualisations
Authors: Sharifian Farzad 
Published: September 2003

AbstractThis paper first elaborates on the notions of conceptualisation and cultural conceptualisations. Cultural conceptualisations enable the members of a cultural group to think, so to speak, in one mind. These conceptualisations are not equally imprinted in the minds of people but are rather represented in a distributed fashion across the minds in a cultural group. Two major kinds of cultural conceptualisations are cultural schemas and cultural categories. These group-level conceptualisations emerge from and act as the locus for the interactions between people from the same cultural background. The members negotiate and renegotiate these conceptualisations across generations. The paper employs the notion of 'distributed representation' in presenting a model of cultural conceptualisations. It then provides examples of such conceptualisations and discusses how they may be instantiated in various artefacts, such as discourse. The paper also proposes a general framework for the identification of cultural conceptualisations, based on the adoption of an ethnographic approach towards the analysis of discourse. Examples from Australian Aboriginal cultural conceptualisations are provided throughout the paper.
The Role of Control in Attributing Intentional Agency to Inanimate Objects
Authors: Barrett Justin , Johnson Amanda Hankes 
Published: September 2003

Abstract
Previous research into the perception of agency has found that objects in twodimensional displays that move along non-inertial-looking paths are frequently attributed intentional agency, including beliefs and desires. The present experiment re-addressed this finding using a tangible, interactive, electromagnetic puzzle. The experimental manipulation was whether or not participants controlled the electromagnet that moved the marbles along unexpected trajectories. Thirty-one college undergraduates participated. Participants who lacked control over the movement of the marbles were significantly more likely to attribute agency to the marbles. Participants in control of the display rarely attributed intentional agency to the marbles. Implications are discussed for the identification of agents in the real world.
Universal prestorage leukoreduction in Canada decreases platelet alloimmunization and refractoriness
Authors: Seftel Matthew D. , Growe Gershon H. , Petraszko Tanya , Benny W. Barrett , Le Alan , Lee Chao-Yong , Spinelli John J. , Sutherland Heather J. , Tsang Peter , Hogge Donna E. 
Published: September 2003

Abstract
Randomized controlled trials have shown a reduction in platelet alloimmunization and refractoriness in patients with acute leukemia (AL) with the use of poststorage leukoreduction of blood products. Universal prestorage leukoreduction (ULR) of red cell and platelet products has been performed in Canada since August 1999. We conducted a retrospective analysis of 13 902 platelet transfusions in 617 patients undergoing chemotherapy (CT) for AL or stem cell transplantation (SCT) before (n = 315) and after (n = 302) the introduction of ULR. Alloimmunization was significantly reduced (19% to 7%, P &lt; .001) in the post-ULR group. Alloimmune platelet refractoriness was similarly reduced (14% to 4%, P &lt; .001). Fewer patients in the post-ULR group received HLA-matched platelets (14% vs 5%, P &lt; .001). Alloimmunization and alloimmune refractoriness in the 318 patients who were previously pregnant and/or transfused were also reduced after ULR (P = .023 and P = .005, respectively). In a Cox regression model, the 3 independent factors that predicted for alloimmune refractoriness were nonleukoreduced blood products (relative risk [RR], 2.2 [95% CI, 1.2-4.3]), a history of pregnancy and/or transfusion (RR, 2.3 [95% CI, 1.3-4.2]), and receipt of 13 or more platelet transfusions (RR, 6.0 [95% CI, 2.4-15.3]). In conclusion, ULR reduces alloimmunization, refractoriness, and requirements for HLA-matched platelets when applied as routine transfusion practice to patients receiving CT or SCT.
Ephrin receptor, EphB4, regulates ES cell differentiation of primitive mammalian hemangioblasts, blood, cardiomyocytes, and blood vessels
Authors: Wang Zhengyu , Cohen Kenneth , Shao Ying , Mole Pamela , Dombkowski David , Scadden David T. 
Published: September 2003

AbstractDifferentiation of pluripotent embryonic stem (ES) cells is associated with expression of fate-specifying gene products. Coordinated development, however, must involve modifying factors that enable differentiation and growth to adjust in response to local microenvironmental determinants. We report here that the ephrin receptor, EphB4, known to be spatially restricted in expression and critical for organized vessel formation, modifies the rate and magnitude of ES cells acquiring genotypic and phenotypic characteristics of mesodermal tissues. Hemangioblast, blood cell, cardiomyocyte, and vascular differentiation was impaired in EphB4–/– ES cells in conjunction with decreased expression of mesoderm-associated, but not neuroectoderm-associated, genes. Therefore, EphB4 modulates the response to mesoderm induction signals. These data add differentiation kinetics to the known effects of ephrin receptors on mammalian cell migration and adhesion. We propose that modifying sensitivity to differentiation cues is a further means for ephrin receptors to contribute to tissue patterning and organization.
Microarray analysis reveals that TP53- and ATM-mutant B-CLLs share a defect in activating proapoptotic responses after DNA damage but are distinguished by major differences in activating prosurvival responses
Authors: Stankovic Tatjana , Hubank Mike , Cronin Debbie , Stewart Grant S. , Fletcher Danielle , Bignell Colin R. , Alvi Azra J. , Austen Belinda , Weston Victoria J. , Fegan Christopher , Byrd Philip J. , Moss Paul A. H. , Taylor A. Malcolm R. 
Published: September 2003

AbstractThe ATM/p53-dependent DNA damage response pathway plays an important role in the progression of lymphoid tumors. Inactivation of the ATM or TP53 gene is frequent in B-cell lymphocytic leukemia (B-CLL) and leads to aggressive disease. Although the ATM and p53 pathways overlap, they are not congruent, and it is unclear how the mechanism of tumor progression differs between ATM- and p53-deficient tumors. Using microarray analysis of ATM-mutant, TP53-mutant, and ATM/TP53 wild-type B-CLLs, we show that after exposure to DNA damage transcriptional responses are entirely dependent on ATM function. The p53 proapoptotic responses comprise only a part of ATM-regulated transcription; additionally, ATM regulates prosurvival responses independently of p53. Consequently, the greater severity of the TP53-mutant B-CLLs compared with ATM-mutant B-CLLs is consistent with the additive effect of defective apoptotic and elevated survival responses after DNA damage in these tumors. We also show that transcription expression profiles of ATM-deficient, TP53-deficient, and wild-type B-CLLs are indistinguishable before irradiation. Therefore, damage-induced transcriptional fingerprinting can be used to stratify tumors according to their biologic differences and simultaneously identify potential targets for treating refractory tumors.
Skewed representation of functionally distinct populations of virus-specific CD4 T cells in HIV-1–infected subjects with progressive disease: changes after antiretroviral therapy
Authors: Harari Alexandre , Petitpierre Stéphanie , Vallelian Florence , Pantaleo Giuseppe 
Published: September 2003

AbstractHIV-1- and cytomegalovirus (CMV)-specific CD4 T-cell-mediated antiviral immunity was evaluated by assessing the frequency of interleukin 2 (IL-2)- and interferon γ (IFN-γ)-secreting cells following antigen-specific stimulation in blood and lymph node. HIV-1-infected subjects with progressive disease at early stage of infection with no previous history of antiretroviral therapy (ART), subjects with nonprogressive disease, and HIV-negative subjects were studied. On the basis of the ability to secrete IL-2 and IFN-γ, 3 functionally distinct populations of CD4 T cells were identified: (1) IL-2-secreting cells; (2) IL-2/IFN-γ-secreting cells; and (3) IFN-γ-secreting cells. CMV-specific CD4 T cells were almost equally distributed within the 3 functionally distinct cell populations in the 3 study groups as well as HIV-1-specific CD4 T cells in subjects with nonprogressive disease. However, a skewing toward IFN-γ-secreting cells (70% of HIV-1-specific CD4 T cells) was observed in subjects with progressive disease, and IL-2- and IL-2/IFN-γ-secreting cells were almost absent. The frequencies of IL-2- and of IL-2/IFN-γ-secreting HIV-1-specific CD4 T cells were negatively correlated with the levels of viremia. Interestingly, prolonged ART was able to correct the skewed representation of different populations of HIV-1-specific CD4 T cells but was associated with only a partial recovery of IL-2-secreting cells. These results indicate that the composition of the pool of functionally distinct virus-specific CD4 T cells is important for virus control. (Blood. 2004;103:966-972)