bluuebunny/crossref_metadata_2025 huggingface dataset:
Psalms, Philippians 2:6-11, and the Origins of Christology
Authors: Collins Adela Yarbro
Published: November 2003

Students of early Christianity recognized long ago that the canonical psalms of the Jewish Bible provided a framework of meaning in which the followers of Jesus could make sense of his crucifixion. This novel hermeneutic is evident in the allusions to the Psalms in the passion narrative of the Gospel according to Mark. It appears also in the Markan Jesus's explanation of the need for the Son of Man to suffer. Most students of the New Testament today understand Philippians 2:6-11 as a pre-Pauline hymn that was composed for early Christian worship. More recent studies suggest that it is exalted prose rather than poetry. The hypothesis of this article is that Paul composed it, either for worship or for the purposes of the argument of his letter to the Philippians. In doing so, he adapted a common social practice of the local culture. The "theologos" was an official in the organized worship of an ancient deity whose duty it was to compose brief speeches, sometimes in prose, sometimes in poetry, in honor of the deity. The organized worship of the emperor included such officials. Paul acted as a "theologos" in writing a brief speech in exalted prose honoring Jesus Christ, whom he had taught the Philippians to honor instead of the emperor.
Narrative Christology and the Son of Man: What the Markan Jesus Says Instead
Authors: Struthers Malbon Elizabeth
Published: November 2003

From the point of view of "narrative christology," not only does the Markan Jesus attempt to deflect attention and honor away from himself and toward God, but he also refracts—or bends—the "christologies" of other characters and the narrator. The image comes from the way a prism refracts "white" light and thus shows its spectral colors. When a thing is bent and looked at from another angle, something different appears. The most obvious way in which the Markan Jesus bends the "christologies" of others is by his statements about the "Son of Man," especially in juxtaposition with "christological titles" offered by other characters and the narrator. No other character or the narrator speaks of the "Son of Man," thus "Son of Man" depicts the Markan Jesus' distinctive point of view. The implied author of Mark challenges the implied audience to deal with the tension between an assertive narrator who proclaims "Jesus Christ, the Son of God" and a reticent Jesus who deflects attention and honor, challenges traditional views, and insistently proclaims not himself but God. To resolve the tension in favor of the narrator (as does Kingsbury) or in favor of the Markan Jesus (as does Naluparyil) would be to flatten the implied author's multi-dimensional narrative and its multi-layered "christology." The implied author of Mark sets up this tension to draw in the implied audienc —not to resolve the tension but to enable hearing of the story of Jesus in its full complexity and mystery.
Die Goldene Regel (Matthäus 7:12/Lukas 6:31) Über den Sitz im Leben ihrer Positiven und uegativen Form
Authors: Theißen Gerd
Published: November 2003

Der Unterschied zwischen der Goldenen Regel in ihrer negativen und positiven Form ist sachlich und historisch für ihr Verständnis relevant. Die negative Form verlangt ein Unterlassen von Handlungen und wird schon in der Antike als universale Forderung gegenüber allen Menschen formuliert. Ihre positive Form, die ein Initiativhandeln verlangt, wird dagegen in vorchristlicher Zeit nur auf besondere soziale Beziehungen, auf das Verhältnis von Freunden, Familienangehörigen und auf den Herrscher bezogen. Feldrede und Bergpredigt machen die positive Form zum Ethos für alle Beziehungen. Sie übertragen damit ein Herrschaftsethos auf kleine Leute und machen ein Verhalten, das oft Freunde und Familienangehörige meinte, zum Verhalten gegen?ber allen Menschen.
Israel's Holy Seed and the Foreign Women of Ezra-Nehemiah: A Kristevan Reading
Authors: Washington Harold
Published: November 2003

Though Ezra 9–10 is written at some distance from the circumstances it represents, the text memorializes at a level more profound than mere historical reportage the predicament of a fragile, emerging Judean subjectivity, a communal—in Kristevan terms—"subject-on-trial." For Kristeva, the biblical language of purity and impurity in Leviticus is already grounded in the abjection of the maternal body. In Ezra's campaign against foreign marriages, however, this repudiation of the feminine is taken a step further. The community's "holy seed" (an umistakably male emblem of purity), is opposed to the pollutions of the peoples of the lands (termed, a specifically female uncleanness). This conjunction of the feminine with the unclean positions women as signifiers of the Judean stranger within; thus only illicit wives (not husbands) and their children are designated for expulsion. Yet the text finally recoils from recounting the dismissal of these women. The divorce assembly scene of Ezra 10 commemorates an agonistic process of Judean self-constitution that remains unresolved for the rest of Ezra-Nehemiah.
The Morning After in Corinth: Bread-and-Butter Notes, Part I
Authors: Bach Alice , Glancy Jennifer
Published: November 2003

Although moralists pined for the days of traditional virtues and simple foodstuffs, the elites of the Roman Empire pursued luxury and excess both in literature and cuisine. Distrust of fancy preparations extended even to the categorization of the constituent elements of diet. James Davidson writes of Greek cuisine, "Victuals were regularly divided into three parts: sitos (the staple, usually bread), opson (whatever one eats with the staple) and poton (drink)." The opson adds nothing and everything, both necessary and unnecessary. No meal is complete without opson, but an ancient proverb held that the very best opson is hunger. Writing to the Corinthian Christians, Paul reminds them that they can fill their bellies at home, with opson, one imagines, and simply gather to share the bread and the wine. Bread and wine suffice. Or do they? Paul proposes a menu: bread, wine, and some words to accompany the sitos and poton. The words of institution serve as an opson; bread and wine are not a banquet without the prescribed words. Paul writes that members of the community have sickened and even died for consuming the Lord's Supper unworthily. Surely it is not the bread and wine that turn their stomachs, but the accompaniment, the opson, the edible words that prove to be lethal. What if the members of the Corinthian community were not, as Paul claims, ill from swallowing the words of institution in an unworthy manner, but rather from the opposite, ingesting the words too literally? An overlooked source of indigestion: the postprandial effects of human flesh and blood.
Revelation, Atonement and the Scope of Faith in the Epistle to the Hebrews: A Deconstructive and Reader-Response Interpretation
Authors: Via Dan
Published: November 2003

Each of three important themes in the Epistle to the Hebrew—the nature of revelation, the rationale of atonement and the scope of saving faith—manifests within itself two divergent or conflicting positions. I have used insights derived from both deconstructive and reader-response criticism to develop an approach for dealing with these tensions. While I have sought not to transgress limits imposed by the historical context of the Epistle, my main concern has been to articulate an interpretation in front of the text.
The Syrians in The Book of the Divided Kingdoms: A Literary/Theological Approach
Authors: Jobling David
Published: November 2003

In earlier work on the Deuteronomic History, I have defined 1 Kings 11 to 2 Kings 17 as 'The Book of the Divided Kingdoms', and argued that its deep-structural 'message' is one of salvation for northern Israel. Here I present the Syrians, the most pervasive foreign presence in this 'Book', as a major element in this dynamic of salvation. In the account of the house of Jehu, they function analogously to the foreign power in one of the judge-cycles (in Judges and 1 Samuel) by means of which Yahweh punishes Israel—a role necessary to the eventual salvation. Historically, it seems likely that all the traditions about the Syrians, and about the prophet Elisha, originated in the time of Jehu's dynasty. But in the existing text, stories of the Syrians and/or Elisha extend well back into the time of Ahab. The reason for this, I suggest, is that the Syrians' salvific role is being intensified by making them agents in the process whereby Baalworship was removed from Israel. In terms of 'ideological geography', Israel's north-east (Syrian) boundary is given a positive valence (cf. traditions of the arrival from that direction of Israel's ancestors), in opposition to the north-west (Tyrian) boundary, whence comes the Baalistic threat. This suggests a promise of salvation even in the later invasions from the north-east, by the Assyrians and their imperial successors.
'Rouzing the Faculties to Act': William Blake, Merkabah Mysticism, the Theology of Liberation and the Exegetical Importance of Experience
Authors: Rowland Christopher
Published: November 2003

This essay is a consideration of the importance of experience and the exegetical possibilities of the allusive nature of the biblical text. It explores the way in which the space was explored by mystics in their visionary experience. In this the interpretative subjects insert themselves into the text as active participants in that which the text describes, so that understanding of the text comes about through experiencing what happens when that imaginative process of identification with the subject matter of the text takes place. The final part of the essay reflects on the way in which, in the modern world, experience of life and the struggle for social justice have informed the way in which the text has functioned as a catalyst for interpretative insight and social change. In the theology of liberation there is a stress on the recognition of the events of one's life and the circumstances in which one lives as ingredients in the exegetical process, so that what one undergoes and learns thereby informs the understanding of the text. The essay is a plea that the widely canvassed view of exegesis which regards it as an exact interpretative science in which meaning can be pinned down by reference to ancient contexts needs to be complemented by a more experienced-based, more imaginative, form of exegesis. What unites these different appeals to experience in exegesis is the importance attached to the contribution of the interpreting subject to exegesis of the biblical text.
Toward a Pastoral Reading of the Bible Not Confined to the Church
Authors: Pixley Jorge
Published: November 2003

Using the experience of the network of popular biblical study groups in Latin America and the biblical scholars who accompany them, this article outlines the basic requirements for a pastoral reading of the Bible. Special emphasis is given to the need for using the history of composition, necessarily hypothetical, in order to recover the political dynamics of the texts. The resulting pastoral reading will serve a public as well as a church function.
Early prediction of outcome and response to alemtuzumab therapy in chronic lymphocytic leukemia
Authors: Rawstron Andy C. , Kennedy Ben , Moreton Paul , Dickinson Anita J. , Cullen Matthew J. , Richards Stephen J. , Jack Andrew S. , Hillmen Peter
Published: November 2003

Alemtuzumab therapy is effective for some refractory chronic lymphocytic leukemia (CLL), but identifying responders requires at least 8 weeks of therapy. Early identification of nonresponders would minimize toxicity and/or facilitate more effective strategies. The aim of this study was to identify a minimally invasive method for early prediction of response and relapse. Flow cytometric monitoring was performed in 887 blood samples and 201 marrow samples from 43 patients undergoing intravenous alemtuzumab therapy. Although the absolute lymphocytosis was resolved in all patients by week 4, significant depletion of bone marrow tumor only occurred if circulating B-lymphocyte counts were persistently less than 0.001 × 109/L, which was rare in nonresponders. The majority of patients (16/28) who did not benefit from a full course of therapy were identified with 100% positive predictive value using the following algorithm: peripheral B-cell count greater than 0.001 × 109/L at week 2 with less than 1 log depletion of circulating B cells between weeks 2 and 4. Monitoring CLL levels after treatment identified patients at risk of early disease progression and could potentially improve patient management. During alemtuzumab therapy, bone marrow CLL depletion only occurs after abrogation of circulating tumor, requiring close monitoring of circulating B-cell levels. If validated in prospective studies, blood monitoring at 2 and 4 weeks may be used to optimize therapy.
PML-RARα is associated with leptin-receptor induction: the role of mesenchymal stem cell–derived adipocytes in APL cell survival
Authors: Tabe Yoko , Konopleva Marina , Munsell Mark F. , Marini Frank C. , Zompetta Claudia , McQueen Teresa , Tsao Twee , Zhao Shourong , Pierce Sherry , Igari Jun , Estey Elihu H. , Andreeff Michael
Published: November 2003

Leptin is secreted by bone marrow (BM) adipocytes and stromal cells and was shown to stimulate myeloid proliferation. We here report that primary acute promyelocytic leukemia (APL) cells express high levels of the leptin-receptor (OB-R) long isoform. In cells with regulated promyelocytic leukemia–retinoic acid receptor (PML-RARα) expression, inducing PML-RARα was found to increase OB-R levels. We then investigated the effects of leptin produced by BM adipocytes on APL cells using a coculture system with mesenchymal stem cell (MSC)–derived adipocytes. In PML-RARα–expressing cells, all-trans retinoic acid (ATRA)– and doxorubicin-induced apoptosis were significantly reduced by coculture with adipocyte-differentiated MSCs. This antiapoptotic effect required direct cell-to-cell interactions, was associated with phosphorylation of signal transducer and activator of transcription-3 (STAT3) and mitogen-activated protein kinase (MAPK), and was reduced by blocking OB-R. This report provides a mechanistic basis for the BM adipocyte–leukemia cell interaction and suggests that OB-R receptor blockade may have therapeutic use in APL.
Distinct pathways of LPS-induced NF-κB activation and cytokine production in human myeloid and nonmyeloid cells defined by selective utilization of MyD88 and Mal/TIRAP
Authors: Andreakos Evangelos , Sacre Sandra M. , Smith Clive , Lundberg Anna , Kiriakidis Serafim , Stonehouse Tim , Monaco Claudia , Feldmann Marc , Foxwell Brian M.
Published: November 2003

How lipopolysaccharide (LPS) signals through toll-like receptors (TLRs) to induce nuclear factor (NF)–κB and inflammatory cytokines in sepsis remains unclear. Major candidates for that process are myeloid differentiation protein 88 (MyD88) and MyD88 adaptor-like/TIR domain-containing adaptor protein (Mal/TIRAP) but their role needs to be further defined. Here, we have examined the role of MyD88 and Mal/TIRAP in primary human cells of nonmyeloid and myeloid origin as physiologically relevant systems. We found that MyD88 and Mal/TIRAP are essential for LPS-induced IκBα phosphorylation, NF-κB activation, and interleukin 6 (IL-6) or IL-8 production in fibroblasts and endothelial cells in a pathway that also requires IKK2. In contrast, in macrophages neither MyD88, Mal/TIRAP, nor IκB kinase 2 (IKK2) are required for NF-κB activation or tumor necrosis factor α (TNFα), IL-6, or IL-8 production, although Mal/TIRAP is still involved in the production of interferon β (IFNβ). Differential usage of TLRs may account for that, as in macrophages but not fibroblasts or endothelial cells, TLR4 is expressed in high levels at the cell surface, and neutralization of TLR4 but not TLR2 blocks LPS signaling. These observations demonstrate for the first time the existence of 2 distinct pathways of LPS-induced NF-κB activation and cytokine production in human myeloid and nonmyeloid cells defined by selective utilization of TLR4, MyD88, Mal/TIRAP, and IKK2, and reveal a layer of complexity not previously expected.
Impaired bone marrow homing of cytokine-activated CD34+ cells in the NOD/SCID model
Authors: Ahmed Forhad , Ings Stuart J. , Pizzey Arnold R. , Blundell Michael P. , Thrasher Adrian J. , Ye Hong T. , Fahey Anne , Linch David C. , Yong Kwee L.
Published: November 2003

The reduced engraftment potential of hematopoietic stem/progenitor cells (HSPCs) after exposure to cytokines may be related to the impaired homing ability of actively cycling cells. We tested this hypothesis by quantifying the short-term homing of human adult CD34+ cells in nonobese diabetic/severe combined immunodeficient (NOD/SCID) animals. We show that the loss of engraftment ability of cytokine-activated CD34+ cells is associated with a reduction in homing of colony-forming cells (CFCs) to bone marrow (BM) at 24 hours after transplantation (from median 2.8% [range, 1.9%-6.1%] to 0.3% [0.0%-0.7%]; n = 3; P < .01), coincident with an increase in CFC accumulation in the lungs (P < .01). Impaired BM homing of cytokine-activated cells was not restored by using sorted cells in G0G1 or by inducing cell cycle arrest at the G1/S border. Blocking Fas ligation in vivo did not increase the BM homing of cultured cells. Finally, we tested cytokine combinations or culture conditions previously reported to restore the engraftment of cultured cells but did not find that any of these was able to reverse the changes in homing behavior of cytokine-exposed cells. We suggest that these changes in homing and, as a consequence, engraftment result from the increased migratory capacity of infused activated cells, leading to the loss of selectivity of the homing process.
Unique SDF-1–induced activation of human precursor-B ALL cells as a result of altered CXCR4 expression and signaling
Authors: Spiegel Asaf , Kollet Orit , Peled Amnon , Abel Loya , Nagler Arnon , Bielorai Bella , Rechavi Gideon , Vormoor Josef , Lapidot Tsvee
Published: November 2003

The mechanisms governing migration and extramedullary dissemination of leukemic cells remain obscure. In this study the migration and in vivo homing to the bone marrow of nonobese diabetic severe combined immunodeficient (NOD/SCID) mice injected with human precursor-B acute lymphoblastic leukemia (ALL) cells in comparison to normal CD34+ progenitors (both cord blood and mobilized peripheral blood) was investigated. Although migration and homing of both cell populations was dependent on stromal cell-derived factor 1 (SDF-1)/CXCR4 interactions, major differences in receptor expression as well as the migratory capacity toward various concentrations of SDF-1 were found. Furthermore, unlike normal CD34+ progenitors, in vivo homing of the leukemic cells was superior when recipient NOD/SCID mice were not irradiated prior to transplantation. In addition, we report differences in the adhesion molecules activated following SDF-1 stimulation, documenting a major role for very late antigen 4 (VLA-4), but not VLA-5 and lymphocyte function-associated antigen-1 (LFA-1), in homing of precursor-B ALL cells. Interestingly, Toxin-B and pertussis toxin inhibited the homing of the leukemic cells but not that of normal CD34+ progenitors or normal CD10+/CD19+ precursor-B cells, revealing differences in CXCR4 signaling pathways that are based on changes that acquired by the leukemic cells. Altogether, our data provide new insights into different SDF-1–induced signaling, activation, and consequent motility between normal CD34+ and precursor-B ALL progenitors, which may lead to improved clinical protocols. (Blood. 2004;103: 2900-2907)
Serum deprivation of human marrow stromal cells (hMSCs) selects for a subpopulation of early progenitor cells with enhanced expression of OCT-4 and other embryonic genes
Authors: Pochampally Radhika R. , Smith Jason R. , Ylostalo Joni , Prockop Darwin J.
Published: November 2003

Recently there has been interest in developing cell and gene therapies with adult stem cells from human bone marrow referred to as mesenchymal stem cells or marrow stromal cells (hMSCs). We incubated early-passage hMSCs in serum-free medium without cytokines or other supplements for 2 to 4 weeks. Surprisingly, a subpopulation of the cells survived serum deprivation and then began to proliferate in serum-containing medium. The cells selected by serum deprivation had longer telomeres than control cells. Also, the patterns of gene expression revealed by reverse transcriptase–polymerase chain reaction (RT-PCR) assays and microarray data indicated that the cells selected by serum deprivation were a subpopulation of very early progenitor cells with enhanced expression of octomer-binding transcription factor 4 (OCT-4) and several other genes characteristically expressed in embryonic cells.
The EOL-1 cell line as an in vitro model for the study of FIP1L1-PDGFRA–positive chronic eosinophilic leukemia
Authors: Cools Jan , Quentmeier Hilmar , Huntly Brian J. P. , Marynen Peter , Griffin James D. , Drexler Hans G. , Gilliland D. Gary
Published: November 2003

We recently identified the chimeric kinase FIP1L1-platelet-derived growth factor receptor α (PDGFRα) as a cause of the hypereosinophilic syndrome and of chronic eosinophilic leukemia. To investigate the role of FIP1L1-PDGFRA in the pathogenesis of acute leukemia, we screened 87 leukemia cell lines for the presence of FIP1L1-PDGFRA. One cell line, EOL-1, expressed the FIP1L1-PDGFRA fusion. Three structurally divergent kinase inhibitors—imatinib (STI-571), PKC412, and SU5614—inhibited the growth of EOL-1 cells. These results indicate that the fusion of FIP1L1 to PDGFRA occurs rarely in leukemia cell lines, but they identify EOL-1 as an in vitro model for the study of FIP1L1-PDGFRA-positive chronic eosinophilic leukemia and for the analysis of small molecule inhibitors of FIP1L1-PDGFRα. (Blood. 2004;103:2802-2805)
Aggretin, a snake venom–derived endothelial integrin α2β1 agonist, induces angiogenesis via expression of vascular endothelial growth factor
Authors: Chung Ching-Hu , Wu Wen-Bin , Huang Tur-Fu
Published: November 2003

Aggretin, a collagen-like α2β1 agonist purified from Calloselasma rhodostoma venom, was shown to increase human umbilical vein endothelial cell (HUVEC) proliferation and HUVEC migration toward immobilized aggretin was also increased. These effects were blocked by A2-IIE10, an antibody raised against integrin α2. Aggretin bound to HUVECs in a dose-dependent and saturable manner, which was specifically inhibited by A2-IIE10, as examined by flow cytometry. Aggretin elicited significant angiogenic effects in both in vivo and in vitro angiogenesis assays, and incubation of HUVECs with aggretin activated phosphatidylinositol 3-kinase (PI3K), Akt, and extracellular-regulated kinase 1/2 (ERK1/2); these effects were blocked by A2-IIE10 or vascular endothelial growth factor (VEGF) monoclonal antibody (mAb). The angiogenic effect induced by aggretin may be via the production of VEGF because the VEGF level was elevated and VEGF mAb pretreatment inhibited Akt/ERK1/2 activation as well as the in vivo angiogenesis induced by aggretin. The VEGF production induced by aggretin can be blocked by A2-IIE10 mAb pretreatment. In conclusion, aggretin induces endothelial cell proliferation, migration, and angiogenesis by interacting with integrin α2β1, leading to activation of PI3K, Akt, and ERK1/2 pathways, and the increased expression of VEGF may be responsible for its angiogenic activity.
Identification of a binding site on human FGF-2 for fibrinogen
Authors: Peng Hu , Sahni Abha , Fay Philip , Bellum Stephen , Prudovsky Igor , Maciag Thomas , Francis Charles W.
Published: November 2003

Endothelial cell adhesive interactions are mediated by both fibrinogen and fibrin, and growth is stimulated by fibroblast growth factor 2 (FGF-2). We have shown previously that FGF-2 binds specifically and with high affinity to fibrinogen and fibrin and that fibrinogen potentiates the proliferative capacity of FGF-2 and also protects it from proteolytic degradation. To further characterize this interaction we have performed FGF-2 mutagenesis to identify the interactive site. Because FGF-1 has a similar structure to FGF-2 but does not bind to fibrinogen, we used a strategy of cassette and site-directed mutagenesis, exchanging residues from FGF-1 and FGF-2 and correlating structural changes with fibrinogen binding. Two cassette interchange mutants, 2212 and 2211, contained either the third cassette or both the third and fourth cassettes from FGF-1, and neither exhibited any affinity for fibrinogen. Exchange of 5 residues (Phe95, Ser100, Asn102, Arg107, and Arg109) from FGF-2 into the corresponding sites in the third cassette of FGF-1 imparted high-affinity binding with apparent dissociation constants (Kd) of 5.3 nM and 8.6 nM, respectively, compared with 1.3 nM for wild-type FGF-2. We conclude that these 5 residues define a high-affinity binding site in FGF-2 for fibrinogen.
Hu1D10 induces apoptosis concurrent with activation of the AKT survival pathway in human chronic lymphocytic leukemia cells
Authors: Mone Andrew P. , Huang Peng , Pelicano Helene , Cheney Carolyn M. , Green Jennifer M. , Tso J. Yun , Johnson Amy J. , Jefferson Sara , Lin Thomas S. , Byrd John C.
Published: November 2003

The 1D10 antigen is the target for Hu1D10 (apolizumab), a humanized HLA-DR β-chain–specific antibody that is currently in clinical trials for hematologic malignancies. We demonstrate that Hu1D10 induces caspase-independent apoptosis following secondary cross-linking in primary chronic lymphocytic leukemia (CLL) cells. Generation of reactive oxygen species (ROS) and signal transduction, as evidenced by phosphorylation of Syk and AKT, were noted. The source of the Hu1D10-induced ROS was examined using the Raji lymphoblastic cell line with engineered defects in the mitochondrial respiratory chain. Hu1D10 treatment of clones with deficient mitochondrial respiration produced ROS suggesting a cytoplasmic source. Administration of ROS scavengers to primary CLL cells prior to Hu1D10 treatment diminished AKT activation. Treatment with Hu1D10 and the phosphatidylinositol 3-kinase inhibitor LY294002 demonstrated in vitro synergy with enhanced apoptosis. In conjunction with an ongoing clinical trial, blood samples were collected following intravenous infusion of Hu1D10 and analyzed for phosphorylation of AKT. Two of 3 patient samples showed a sustained increase in AKT phosphorylation following Hu1D10 administration. These data suggest that Hu1D10 ligation in CLL cells induces death and survival signals for which combination therapies may be designed to greatly enhance efficiency of both Hu1D10 and other class II antibodies in development.
Comparative cytokine profile of human skin mast cells from two compartments—strong resemblance with monocytes at baseline but induction of IL-5 by IL-4 priming
Authors: Babina Magda , Guhl Sven , Stärke André , Kirchhof Loreen , Zuberbier Torsten , Henz Beate M
Published: November 2003

Although known as heterogenous, mast cells (MC) are believed to induce allergic inflammation, partially by secretion of T helper cell type 2 (Th2) cytokines. We show here that MC purified from twohuman skin compartments produce cytokines that are primarily associated with inflammation and innate immunity [interleukin (IL)-1β, IL-6, IL-8, tumor necrosis factor α (TNF-α)]. Although these are detectable even without stimulation, immunoglobulin (Ig)E receptor cross-linking is able to enhance only TNF-α production, but phorbol 12-myristate 13-acetate additionally promotes IL-1β and IL-8. With the exception of TNF-α, the presence of serum has a positive impact on cytokine production. Although IL-13 transcripts (but not those for IL-4 and -5) are produced by skin MC, all Th2 cytokines remain undetectable in the supernatants or lysates of MC from foreskin and breast skin by all treatments. Therefore, rather than sharing similarity with Th2 cells, the cytokine profile of skin MC at baseline resembles that of monocytes. Of note, MC precultured in the presence of IL-4 [alone or plus stem cell factor (SCF)] before anti-IgE stimulation, acquired the ability to produce IL-5, and IL-1β was concomitantly suppressed. Additionally, strong up-regulation of IL-6 by SCF was observed, which was inhibited by IL-4. In summary, we present a detailed analysis of the cytokine array of human skin MC immediately upon isolation; demonstrate that MC from different skin compartments, although producing the same pattern of cytokines, display quantitative differences in several aspects; and provide further evidence that MC possess a proinflammatory capacity, which can, however, be altered by microenvironmental stimuli, substantiating the marked plasticity of the cells.
Gene-expression profiling of CD34+ cells from various hematopoietic stem-cell sources reveals functional differences in stem-cell activity
Authors: Ng Yuk Yin , van Kessel Berris , Lokhorst Henk M , Baert Miranda R M , van den Burg Caroline M M , Bloem Andries C , Staal Frank J T
Published: November 2003

The replacement of bone marrow (BM) as a conventional source of stem cell (SC) by umbilical cord blood (UCB) and granulocyte-colony stimulating factor-mobilized peripheral blood SC (PBSC) has brought about clinical advantages. However, several studies have demonstrated that UCB CD34+ cells and PBSC significantly differ from BM CD34+ cells qualitatively and quantitatively. Here, we quantified the number of SC in purified BM, UCB CD34+ cells, and CD34+ PBSC using in vitro and in vivo assays for human hematopoietic SC (HSC) activity. A cobblestone area-forming cell (CAFC) assay showed that UCB CD34+ cells contained the highest frequency of CAFCwk6 (3.6- to tenfold higher than BM CD34+ cells and PBSC, respectively), and the engraftment capacity in vivo by nonobese diabetic/severe combined immunodeficiency repopulation assay was also significantly greater than BM CD34+, with a higher proportion of CD45+ cells detected in the recipients at a lower cell dose. To understand the molecular characteristics underlying these functional differences, we performed several DNA microarray experiments using Affymetrix gene chips, containing 12,600 genes. Comparative analysis of gene-expression profiles showed differential expression of 51 genes between BM and UCB CD34+ SC and 64 genes between BM CD34+ cells and PBSC. These genes are involved in proliferation, differentiation, apoptosis, and engraftment capacity of SC. Thus, the molecular expression profiles reported here confirmed functional differences observed among the SC sources. Moreover, this report provides new insights to describe the molecular phenotype of CD34+ HSC and leads to a better understanding of the discrepancy among the SC sources.
The spreading of B lymphocytes induced by CD44 cross-linking requires actin, tubulin, and vimentin rearrangements
Authors: Sumoza-Toledo Adriana , Santos-Argumedo Leopoldo
Published: November 2003

CD44 is a polymorphic family of adhesion molecules widely distributed on cells and tissues. CD44 is up-regulated on activated lymphocytes, and it can function as a receptor, mediating rolling and migration. Although it has been demonstrated that anti-CD44 antibodies bound to tissue-culture plates induce multidirectional emission of retractile dendrites (“spreading”) in activated murine B lymphocytes, the involvement of cytoskeleton elements in this phenomenon is largely unknown. In this work, it is shown that the generation of dendrites induced by CD44 cross-linking in activated B cells depends on actin, microtubules, and vimentin reorganization. Immunofluorescence analysis showed that dendrite formation began with actin polymerization, and its extension was favored by microtubules and intermediate filaments of vimentin oriented to the polymerized actin. Pretreatment of activated B lymphocytes with cytochalasin E inhibited the dendrites formation; moreoer, when cells were treated with this drug at different time points during the dendrite formation process, the stability of the dendrites was affected. In contrast, although the treatment with colchicine and nocodazole (tubulin polymerization inhibitors) inhibited the dendrites formation, it did not inhibit the initial phase of actin polymerization. According to these results, B cell spreading and dendrite formation induced by anti-CD44 antibodies require coordinated rearrangements of actin, microtubules, and vimentin, being the actin cytoskeleton, the most important element that confers stability and drives the morphological changes during B cell spreading, conceivably preparing B lymphocytes for locomotion.
Embryonic signals direct the formation of tight junctional permeability barrier in the decidualizing stroma during embryo implantation
Authors: Wang Xiaohong , Matsumoto Hiromichi , Zhao Xuemei , Das Sanjoy K. , Paria Bibhash C.
Published: November 2003

The protection of the embryo from the maternal adverse environment during early pregnancy is considered to be achieved by the establishment of a transitory permeability barrier created by decidual cells immediately surrounding the implanting embryo. Normally, the polarized epithelium acts as a barrier by regulating paracellular passage of substances through tight junctions. The expression of tight junction proteins in the uterine luminal epithelium prior to implantation is consistent with this idea. However, limited information is available regarding the nature and regulation of the permeability barrier that is created by decidualizing stromal cells during implantation. We show here that the tight junction proteins, occludin, claudin-1, zonula occludens-1 and zonula occludens-2, are all expressed and physically associated in decidualizing stromal cells of the primary decidual zone forming a barrier surrounding the embryo with the loss of adjacent luminal epithelium. The blastocyst trophectoderm appears to be the stimulus for the creation of this barrier, since isolated inner cell mass or artificial stimuli failed to induce such a barrier. Furthermore, the primary decidual zone induced by the normal blastocyst is impermeable to immunoglobulin molecules. These findings suggest that trophoblast-induced expression of tight junctions forms a temporary barrier in cells of the primary decidual zone that restricts the passage of injurious stimuli such as maternal immunoglobulins to the embryo.
Self-assembling Lipid Microtubules Based on Cyclobolaphile That Mimics Archaeal Membrane Lipid
Authors: Miyawaki Kazuhiro , Goto Rie , Shibakami Motonari
Published: November 2003

This paper describes the first preparation of lipid microtubules that are composed of macrocyclic lipids. The lipid contains diacetylenic alkyl chains in a hydrophobic segment and phosphatidylcholine as a hydrophilic headgroup. The structural features of the assembly include: (i) monolayer wall, (ii) micron scale length, (iii) nano scale diameter, and (iv) elasticity.
New Donor–Acceptor 2-Aryl-3-(4-pyridyl)-2,5-norbornadienes as Thermally Reversible Photochromic Systems
Authors: Elangovan Arumugasamy , Wang Chieh-Ju , Ho Tong-Ing
Published: November 2003

New donor–acceptor 2,3-diarylnorbornadienes (1N–4N) showing high quantum yields for the blue light induced valence isomerization from the norbornadienes into quadricyclanes and the latters’ thermal reversion are studied in comparison with their protonated counterparts.
Morphological Studies on Well-defined Polyethylene-b-poly(ethylene-co-propylene) by AFM
Authors: Ono Shoko S , Matsugi Tomoaki , Matsuoka Osamu , Kojoh Shin-ichi , Fujita Terunori , Kashiwa Norio , Yamamoto Sadaaki
Published: November 2003

Morphology of a well-defined polyethylene-b-poly(ethylene-co-propylene) (PE-b-EPR) on a mica surface was analyzed by atomic force microscopy (AFM). The analyses suggested that the block copolymer, in which the PE lamella is covered with the amorphous EPR segment, can exist without aggregation and possesses a tendency to assemble to one another to form a needle-like structure.
Surgical Resection of Unilateral Lung Metastases: Is Bilateral Thoracotomy Necessary?
Authors: Younes Riad N. , Gross Jefferson L. , Deheinzelin Daniel
Published: November 2003

urgical resection of lung mestastases is routine procedure for selected patients with pulmonary nodules and solid tumors. In some cases, patients present with unilateral pulmonary metastases amenable to surgical resection. Surgeons are still divided between unilateral approach directed to the radiologically detected nodules, or bilateral exploratory thoracotomy. This study evaluates the need for bilateral thoracotomy in patients diagnosed with unilateral lung metastases. A retrospective evaluation was made of a prospective database from a single institution (1990–1997)
of all consecutive patients (n = 267) diagnosed on admission with unilateral (n = 179) or bilateral (n= 88) lung nodules. Ipsilateral thoracotomy was performed on all patients with unilateral disease. Bilateral thoracotomy was performed on all patients with bilateral lung metastases.
Histology: adenocarcinoma (25%), osteosarcoma (23%), squamous cell carcinoma
(18%), soft‐tissue sarcoma (18%), and other (16%). Median follow‐up was 17
months. Contralateral disease‐free survival and overall survival were determined. Univariate and multivariate analyses were performed to determine prognostic factors for overall and contralateral disease‐free survival. The two groups of patients with confirmed bilateral metastases (synchronous or metachronous) were compared. Actuarial overall 5‐year survival was 34.9%.
Contralateral recurrence‐free 6‐month, 12‐month, and 5‐year survival were 95%,
89%, and 78%, respectively. Patients who experienced recurrence in the contralateral lung within 3, 6, or 12 months had an overall 5‐year survival rate of 24%, 30%, and 37%, respectively. When patients with recurrence in the contralateral lung were compared to patients with bilateral metastases on admission, there was no significant difference in overall survival. Only histology and the number of pathologically proven metastases significantly
(p <0.05) predicted recurrence in the contralateral lung. Bilateral exploration of unilateral lung metastases is not warranted in all cases. Most patients will have only unilateral disease, and delaying contralateral thoracotomy until disease is detected radiologically does not appear to affect outcome.
High Grade Dysplasia: Surveillance, Mucosal Ablation, or Resection?
Authors: Korst Robert J. , Altorki Nasser K.
Published: November 2003

Barrett’s esophagus is a common premalignant condition that results from chronic gastroesophageal reflux. High grade dysplasia in the metaplastic esophagus is thought to be the last step in the metaplasia‐to‐carcinoma sequence that characterizes this disease. The management of high grade dysplasia in Barrett’s esophagus is controversial. Some investigators advocate a rigorous endoscopic surveillance program with biopsies, but this approach has been questioned because of its clinical impracticality, high cost, possibility of sampling errors, and difficulty demonstrating effectiveness on a reproducible basis. Others advocate mucosal ablative therapy to eradicate the dysplastic and metaplastic epithelium. This approach, still in its infancy, cannot be accepted as standard therapy at the present time because of limited follow‐up, its questionable ability to completely eradicate the abnormal mucosa, the phenomenon of pseudoregression, and the patients require continued rigorous endoscopic surveillance. Esophagectomy, on the other hand, can be accomplished with a low mortality rate in these patients. We advocate this approach because a large number of them have invasive cancer in the esophagus despite a preoperative diagnosis of only high grade dysplasia. In addition, the 5‐year survival is excellent even if invasive cancer is present, and these patients are liberated from rigorous endoscopic surveillance for the rest of their lives. For patients with high grade dysplasia in Barrett’s esophagus who are poor operative risks, less invasive approaches such as mucosal ablation may play a role, but longer follow‐up information is needed before this technique can be accepted even in this setting.
Collaboration, Communication, Management, and Advocacy: Teaching Surgeons New Skills through the CanMEDS Project
Authors: Frank Jason R. , Langer Bernard
Published: November 2003

The training of future surgeons must evolve in such a way that it ensures that surgical practice meets the needs of modern societies. Many surgical educators and organizations are considering which abilities are critical elements of the education of surgeons for the new millennium. We describe the approach employed by the Royal College of Physicians and Surgeons of Canada (RCPSC), called the Canadian Medical Education Directions for Specialists (CanMEDS) Project. Through this endeavor the RCPSC has adopted a framework of core competencies organized around seven physician “Roles”: Medical Expert, Communicator, Collaborator, Manager, Health Advocate, Scholar, and Professional. We present the development and rationale for this framework and the progress of its implementation in postgraduate surgical training programs across Canada.
Paranasal Sinus Cancer: Caveats and Controversies
Authors: Waldron John , Witterick Ian
Published: November 2003

Paranasal sinus cancer is a very rare disease. The literature contains numerous small retrospective reports describing the treatment and outcome of these patients. The comparison of patient outcome both within and between these reports is hampered by patient heterogeneity. We have outlined some of the caveats to be kept in mind when interpreting this literature and described some of the resultant controversies. The failure to achieve local control of advanced disease remains a major problem. Strategies for improvement of local control will include advanced surgical techniques with radiation dose escalation using state‐of‐the‐art, high‐precision delivery techniques accompanied by concurrent cytotoxic and/or biologic therapies. The ideal integration of surgery and radiation remains to be defined in the context of contemporary treatment approaches designed to achieve optimum local control and organ preservation.
Pre‐surgery knee joint loading patterns during walking predict the presence and severity of anterior knee pain after total knee arthroplasty
Authors: Smith Anne J. , Lloyd D. G. , Wood D. J.
Published: November 2003

This study tested if abnormal sagittal knee joint loading patterns after total knee arthroplasty (TKA) were present pre‐surgery, and if patterns with higher external knee flexion moments were related to the presence and severity of post‐surgery anterior knee pain. Gait analysis and clinical evaluation were performed on 34 patients (41 arthroplasties) both before and 12–18 months after TKA, and on 20 healthy age‐matched controls at matched velocities. The majority of knees with abnormal flexor or extensor sagittal knee joint loading patterns post‐surgery (18 of 26, 69%) also displayed these patterns pre‐surgery. Knee joint loading in the early mid‐stance phase of walking prior to surgery was identified by stepwise regression as a significant predictor of the presence (exp(β) = 2.9, CI: 1.2–6.8, p = 0.017) and severity of post‐surgery anterior knee pain (R2 = 0.314, p = 0.019). Therefore, the frequency and severity of anterior knee pain after TKA can be partially explained by retained pre‐surgery gait patterns that had higher external flexion moments in the early mid‐stance phase, which place higher forces on the patellofemoral joint. © 2003 Orthopaedic Research Society. Published by Elsevier Ltd. All rights reserved.
FREEDOM TO CHOOSE AND DEMOCRACY
Authors: Przeworski Adam
Published: November 2003

Should democracts value the freedom to choose? Do people value facing distinct choices when they make collective decisions? ‘Autonomy’ – the ability to participate in the making of collective decisions – is a paltry notion of freedom. True, democrats must be prepared that their preferences may not be realized as the outcome of the collective choice. Yet democracy is impoverished when many people cannot even vote for what they most want.

‘The point is not to be free, but to act freely.’ Rosa Luxemburg
A transferability study of model parameters for the variable infiltration capacity land surface scheme
Authors: Huang Maoyi , Liang Xu , Liang Yao
Published: November 2003

In this paper, a framework for transferring model parameters from data‐rich areas to data‐sparse areas is presented. The study shows that there are two critical steps for the success of transferring model parameters in general. The first is to effectively classify basic available data into clusters, and the second is to establish nonlinear relationships between model parameters and the classified basic available data. The framework for transferring model parameters is illustrated with the b‐parameter of the Variable Infiltration Capacity (VIC) land surface model. The b‐parameter, which controls the shape of spatial distribution of soil moisture capacity for a study area, usually cannot be directly measured. At present, the VIC b‐parameter is generally estimated through model calibration, which is not feasible for applications of regional climate and general circulation model studies because of limited observations. Therefore, to transfer the b‐parameter from data‐rich to data‐sparse areas, an effective approach for estimating the b‐parameter for the data‐rich areas is necessary. In this paper, we present an alternative approach to estimate the b‐parameter values using the State Soil Geographic (STATSGO) database. The methodology of transferring the VIC b‐parameter from data‐rich areas to data‐sparse areas combines a self‐organizing map neural network with a K‐means clustering method to classify soil data based on soil characteristics. A supervised neural network using a Bayesian regularization method is then developed to describe the nonlinear relationships between the VIC b‐parameter and the statistics of soil properties. The framework is tested using soil data from Arkansas, California, Oklahoma, and Texas with encouraging results. A case study at the Illinois River watershed near Watts is carried out to evaluate the impact of the presented parameter transferability framework on model performance. The initial result shows that the b‐parameter estimated from the proposed transferability framework provides reasonable model‐simulated streamflows when compared to the observations.
A minimum thermodynamic model for the bipolar seesaw
Authors: Stocker Thomas F. , Johnsen Sigfùs J.
Published: November 2003

The simplest possible model is proposed to explain a large fraction of the millennial climate variability measured in the isotopic composition of Antarctic ice cores. The model results from the classic bipolar seesaw by coupling it to a heat reservoir. In this “thermal bipolar seesaw” the heat reservoir convolves northern time signals with a characteristic timescale. Applying the model to the data of GRIP and Byrd, we demonstrate that maximum correlation can be obtained using a timescale of about 1000–1500 years. Higher correlations are obtained by first filtering out the long‐term variability which is due to astronomical and greenhouse gas forcing and not part of the thermal bipolar seesaw. The model resolves the apparent confusion whether northern and southern climate records are in or out of phase, synchronous, or time lagged.