bluuebunny/crossref_metadata_2025_split huggingface dataset:
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

AbstractHow 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

Abstract
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 &lt; .01), coincident with an increase in CFC accumulation in the lungs (P &lt; .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

AbstractThe 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

AbstractRecently 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

Abstract
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

AbstractAggretin, 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

AbstractEndothelial 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

AbstractThe 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

AbstractAlthough 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

AbstractThe 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

AbstractCD44 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.
Self-assembling Lipid Microtubules Based on Cyclobolaphile That Mimics Archaeal Membrane Lipid
Authors: Miyawaki Kazuhiro , Goto Rie , Shibakami Motonari 
Published: November 2003

Abstract
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

Abstract
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

Abstract
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

Abstracturgical 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.