bluuebunny/crossref_metadata_2025_split huggingface dataset:
Spins as probes of different electronic states
Authors: Suter Dieter , Klieber Robert 
Published: March 2007

AbstractNuclear spins are efficient probes of electronic states. Because most NMR experiments are performed in thermal equilibrium, they probe the electronic ground state—the only state that is significantly populated under ambient conditions. Probing electronically excited states becomes possible, if magnetic resonance techniques are combined with optical (laser) excitation. Depending on the nature of the electronic state, drastic changes of the magnetic resonance parameters may be observed. We discuss the basic principles of this type of investigation. Depending on the lifetime of the electronically excited state, it is possible to measure separate spectra of ground and excited state if the lifetime is long on the NMR timescale, or an averaged spectrum if the lifetime is short. We present examples for both limiting cases using rare earth ions and semiconductor heterostructures. © 2007 Wiley Periodicals, Inc. Concepts Magn Reson Part A 30A: 116–126, 2007.
Upfront window trial of topotecan in previously untreated children and adolescents with poor prognosis metastatic osteosarcoma
Authors: Seibel Nita L. , Krailo Mark , Chen Zhengjia , Healey John , Breitfeld Philip P. , Drachtman Richard , Greffe Brian , Nachman James , Nadel Helen , Sato Judith K. , Meyers Paul A. , Reaman Gregory H. 
Published: March 2007

AbstractBACKGROUND.Patients with metastatic osteosarcoma have a poor prognosis. The objectives of the study were to determine the antitumor activity and toxicity of topotecan (daily ×5) in newly diagnosed patients with metastatic osteosarcoma followed by chemotherapy (ifosfamide, carboplatin, etoposide [ICE], alternating with cisplatin and doxorubicin [CD]).METHODS.Newly diagnosed patients (≤30 years of age) with extensive metastatic disease (primary and ≥5 pulmonary nodules and/or bone metastases) with normal hepatic, renal, and cardiac function were eligible. Patients were eligible to receive further topotecan after standard chemotherapy if they exhibited a response. Twenty‐eight patients were enrolled. Seventeen had metastases to the lung only and 11 had metastases to the bone or multiple sites. Of 28 patients enrolled, 27 could be evaluated for response. A limited dose escalation was incorporated.RESULTS.No responses were seen in the 11 patients treated at 3 mg/m2/day. One partial response (PR) and 1 clinical response (CLR) were reported among 15 patients who received topotecan at 3.5 mg/m2/day. No dose‐limiting toxicity was observed. Principal nondose‐limiting toxicities were hematologic and gastrointestinal. The 2‐ and 5‐year event‐free survival rates were low, 7% and 4%, respectively, but the 2‐ and 5‐year overall survival rates were 44% and 22%, respectively.CONCLUSIONS.Topotecan at dose of 3.5 mg/m2/day can be safely administered upfront to newly diagnosed patients without excessive toxicity. Insufficient activity was seen with topotecan in this schedule to warrant further studies in osteosarcoma. The combination of ICE and CD was tolerable when delivered after initial topotecan therapy. Cancer 2007. © 2007 American Cancer Society.
Emerging roles for zic genes in early development
Authors: Merzdorf Christa S. 
Published: March 2007

AbstractMembers of the Zic family of zinc finger transcription factors play critical roles in a variety of developmental processes. They are involved in development of neural tissues and the neural crest, in left‐right axis patterning, in somite development, and in formation of the cerebellum. In addition to their roles in cell‐fate specification, zic genes also promote cell proliferation. Further, they are expressed in postmitotic cells of the cerebellum and in retinal ganglion cells. Efforts to determine the role of individual zic genes within an array of developmental and cellular processes are complicated by overlapping patterns of zic gene expression and strong sequence conservation within this gene family. Nevertheless, substantial progress has been made. This review summarizes our knowledge of the molecular events that govern the activities of zic family members, including emerging relationships between upstream signaling pathways and zic genes. In addition, advancements in our understanding of the molecular events downstream of Zic transcription factors are reviewed. Despite significant progress, however, much remains to be learned regarding the mechanisms through which zic genes exert their function in a variety of different contexts. Developmental Dynamics 236:922–940, 2007. © 2007 Wiley‐Liss, Inc.
Pan‐myocardial expression of Cre recombinase throughout mouse development
Authors: Breckenridge Ross , Kotecha Surendra , Towers Norma , Bennett Michael , Mohun Tim 
Published: March 2007

AbstractMouse‐lines expressing Cre recombinase in a tissue‐specific manner are a powerful tool in developmental biology. Here, we report that a 3 kb fragment of the Xenopus laevis myosin light‐chain 2 (XMLC2) promoter drives Cre recombinase expression in a cardiac‐restricted fashion in the mouse embryo. We have isolated two XMLC2‐Cre lines that express recombinase exclusively within cardiomyocytes, from the onset of their differentiation in the cardiac crescent of the early embryo. Expression is maintained throughout the myocardium of the embryonic heart tube and subsequently the mature myocardium of the chambered heart. Recombinase activity is detected in all myocardial tissue, including the pulmonary veins. One XMLC2‐Cre line shows uniform expression while the other only expresses recombinase in a mosaic fashion encompassing less than 50% of the myocardial cells. Both lines cause severe cardiac malformations when crossed to a conditional Tbx5 line, resulting in embryonic death at midgestation. Optical projection tomography reveals that the spectrum of developmental abnormalities includes a shortening of the outflow tract and its abnormal alignment, along with a dramatic reduction in trabeculation of the ventricular segment of the looping heart tube. genesis 45:135‐144, 2007. © 2007 Wiley‐Liss, Inc.
Influence of interleukin‐6 (IL‐6) autoantibodies on IL‐6 binding to cellular receptors
Authors: Hansen Morten Bagge , Svenson Morten , Abell Kathrine , Yasukawa Kiyoshi , Diamant Marcus , Bendtzen Klaus 
Published: March 2007

AbstractNeutralizing autoantibodies to interleukin‐6 (aAb‐IL‐6) have been reported in healthy individuals, in patients with autoimmune diseases, and in pharmaceutically prepared pooled IgG (IVIg). We investigated the ability of aAb‐IL‐6 derived from IVIg to interfere with IL‐6 binding to the undifferentiated monocytic cell line U‐937. High‐affinity aAb‐IL‐6, primarily of the IgG1 subclass, constituted approximately 1:106 of the total IgG in IVIg preparations. IL‐6 binding to cellular receptors was strongly inhibited by one class of aAb‐IL‐6. These antibodies recognized epitope(s) on IL‐6 essential for the binding of IL‐6 to the α subunit of the IL‐6 receptor (IL‐6R). Another class of aAb‐IL‐6 recognized epitope(s) on IL‐6, which is not essential for the binding to IL‐6R but nevertheless important for the formation of high‐affinity cellular IL‐6 binding. These antibodies presumably interfered with the association of IL‐6 receptor β chains (gp130) with IL‐6/IL‐6R complexes, implicating that small IL‐6/aAb‐IL‐6 immune complexes bound saturably (low affinity/high capacity) to cellular IL‐6 receptors. There was no detectable binding of IL‐6 through aAb‐IL‐6 and Fc receptors on U‐937, and IVIg had no direct IL‐6 receptor antagonizing activity. Dissociation kinetics of IL‐6/aAb‐IL‐6 complexes at 37 °C revealed that IL‐6 was liberated from 75% of the aAb‐IL‐6 with a half‐time (t/2) ≈ 4 h but bound almost irreversibly to the remaining aAb‐IL‐6 (t/2 > 20 h). Cellular IL‐6 uptake and degradation was suppressed by aAb‐IL‐6. Taken together, the data suggest that loss of immunologic tolerance against IL‐6 might be a novel physiological mechanism by which IL‐6 activities are effectively attenuated. Finally, binding of IL‐6 in complex with IgG1 aAb‐IL‐6 on cells expressing IL‐6 receptors implicates that such cells could be targets of antibody‐dependent immunological reactions, including cytotoxic reactions.
Murine macrophage scavenger receptor: in vivo expression and function as receptor for macrophage adhesion in lymphoid and non‐lymphoid organs
Authors: Hughes Derralynn A. , Fraser Iain P. , Gordon Siamon 
Published: March 2007

AbstractMacrophage scavenger receptors are trimeric integral membrane glycoproteins which have been implicated in various macrophage functions including uptake of oxidized lipoprotein and the serum‐dependent, divalent cation‐independent adhesion of macrophages to tissue culture‐treated plastic. In this study we have used a recently defined monoclonal antibody (2F8) which recognizes murine macrophage scavenger receptor, to explore its expression in lymphoid and non‐lymphoid organs of the normal adult. Scavenger receptor was detected in the red pulp and marginal zone of normal adult mouse spleen, medulla of the thymus and subcapsular region of lymph nodes. Kupffer cells in the liver, alveolar macrophages in the lung and lamina propria macrophages in the gut all reacted with 2F8 monoclonal antibody. The antigen was not detected on any nonmacrophage cells, with the exception of sinusoidal endothelial cells in the liver. In the spleen, lymph node and liver, scavenger receptor antigen expression was associated specifically with phagocytic cells which had taken up colloidal carbon.To examine macrophage adhesion in a context relevant to the interactions occurring within lymphoid and non‐lymphoid organs, and the contribution of macrophage scavenger receptor to this adhesion, we designed an assay of macrophage adhesion to frozen tissue sections. Adhesion to most tissues was high and uniform in the absence of any chelating agents. The chelation of Ca2+ and Mg2+ revealed specific patterns of macrophage adhesion in lymphoid and non‐lymphoid organs which was completely inhibited by 2F8. The ability of this antibody to block the EDTA‐resistant adhesion correlated with tissue expression of the antigen in some tissues. Unlike adhesion to tissue culture‐treated plastic, macrophage scavenger receptor‐dependent adhesion of macrophages to frozen tissue sections did not exhibit an absolute requirement for exogenous fetal bovine serum indicating the presence of an endogenous ligand for scavenger receptor within the tissues. We propose that macrophage scavenger receptor is a candidate homing or retention molecule for macrophage localization within ligand‐rich tissues.
Acute rejection of vascular heart allografts by perforin‐deficient mice
Authors: Schulz Manfred , Schuurman Henk‐Jan , Joergensen Joanne , Steiner Carolina , Meerloo Timo , Kägi David , Hengartner Hans , Zinkernagel Rolf M. , Schreier Max H. , Bürki Kurt , Ledermann Birgit 
Published: March 2007

AbstractTo study the role of perforin in cell‐mediated graft rejection, vascularized hearts were grafted to perforin‐deficient C57BL/6 and control C57BL/6 recipient mice. Fully allogeneic heart grafts (BALB/c) were acutely rejected by both recipients within 6 days. Peritoneal exudate lymphocytes from control mice but not from perforin‐deficient mice exhibit a strong alloreactive cytotoxic activity in vitro. Histological analysis of the rejected tissues demonstrated extensive mononuclear cell infiltrates in both recipients. Flow cytometry analysis and immunohistology of graft‐infiltrating cells showed similar proportions of lymphocyte subsets (CD8 ≧ CD4). Collectively, these data indicate that perforin is not essential in the cell‐mediated acute rejection of a fully mismatched heart allograft. However, perforin‐dependent effector mechanisms appeared to be limiting in the T cellmediated rejection of heart allografts differing only at a single major histocompatibility complex class I antigen (bm1), because these grafts survived longer (mean 87.8 days) in perforin‐deficient than in control mice (mean 31.5 days).
Regulation of 4‐1BB expression by cell‐cell interactions and the cytokines, interleukin‐2 and interleukin‐4
Authors: Pollok Karen E. , Kim Seung H. , Kwon Byoung S. 
Published: March 2007

Abstract4‐1BB expression increased gradually following T cell activation, and by day 3 post‐stimulation with immobilized anti‐CD3 (anti‐CD3i) or concanavalin A (Con A), splenic T cells were routinely 35–45% 4‐1BB+ by flow cytometric analysis. 4‐1BB was expressed on activated CD8+, CD4+, CD28+ and CD45RB+ T cells. Optimal 4‐1BB expression was seen by day 6 post‐stimulation and was cell density dependent. When T cells were cultured for 6 days at 1 × 106/well in a 24‐well plate with anti‐CD3i, 82% of the cells were 4‐1BB+. In contrast, at lower cell densities (4 × 105, 2 × 105 and 1 × 105), optimal 4‐1BB expression was observed only if the cultures were supplemented with recombinant interleukin‐2 (IL‐2) or recombinant IL‐4 (IL‐4). In agreement, with these results, modes of inducing endogenous IL‐2 production such as cross‐linking the costimulatory molecule, CD28, or the addition of syngeneic accessory cells to T cells activated with anti‐CD3i, resulted in high levels of 4‐1BB expression. The addition of interleukin‐1α(IL‐1α) or interferon‐γ (IFN‐γ) did not increase 4‐1BB expression on anti‐CD3i‐activated T cells. In addition, if T cells were incubated with IL‐2, IL‐4, IL‐1α, IFN‐γ or anti‐CD28 alone, no 4‐1BB expression was induced. T cells activated with soluble anti‐CD3 (anti‐CD3s) in the presence of IL‐2, IL‐4, or accessory cells, did not express higher levels of 4‐1BB on their cell surface. These data suggest that initial events crucial for efficient T cell activation, such as signals delivered through the T cell receptor/CD3 complex and the CD28 molecule, are instrumental in regulating subsequent 4‐1BB expression.
Cytokine expression and regulation of human plasma cells: disappearance of interleukin‐10 and persistence of transforming growth factor‐β1
Authors: Matthes Thomas , Werner‐Favre Christiane , Zubler Rudolf H. 
Published: March 2007

AbstractLess is known about the cytokine expression and regulation of normal plasma cells compared to that of activated B cells or myeloma cells. This study shows that nonproliferating (hydroxyurea‐treated), immunoglobulin (Ig)‐secreting cells generated from human B cells in the EL‐4 culture system no longer express interleukin (IL)‐6 mRNA, progressively lose IL‐10 mRNA, but continue to express transforming growth factor (TGF)‐β1 mRNA. Secretion of TGF‐β1 protein was demonstrated. On the other hand, and in contrast to the suppression of B cell proliferation and Ig secretion, the basal or the IL‐6/IL‐10 stimulated Ig secretion of nonproliferating cells was not inhibited by recombinant TGF‐γ1. Plasma cells isolated from human bone marrow expressed neither IL‐6 nor IL‐10 mRNA; only TGF‐β1 mRNA was detected by reverse transcription–polymerase chain reaction analysis. Such plasma cells may be on average more “aged” cells than those generated in vitro. Thus, plasma cells persistently express TGF‐β1, a known suppressor of various lymphoid and hemopoietic cell activities, but do not limit their own Ig secretion via this cytokine.
Location and sequence of rearranged immunoglobulin genes in human thymus
Authors: Dunn‐Walters Deborah K. , Howe Caroline J. , Isaacson Peter G. , Spencer Jo 
Published: March 2007

AbstractThymic B cells are a proliferating B cell population concentrated in normal thymic medulla. They are large cells, some with dendritic morphology, and are not associated with any organized follicular structure. Previous work in this laboratory has shown that most of these B cells are surrounded by tightly adherent thymocytes. The literature on human thymic B cells contains many inconsistencies. There is no consensus on whether they express CD5. Even the existence of thymic B cells has been questioned. In this study we have undertaken the first analysis of rearranged immunoglobulin (Ig) genes, looking in particular for evidence of affinity maturation. The Ig VH genes of human thymic B cells in this study are those of the fetal repertoire, though the resemblence to fetal Ig genes is limited in other respects. They are mostly unmutated, but the presence of mutated sequences suggests that this is not a uniform population, as has been previously indicated by phenotypic studies.
Inhibition of CD28‐mediated T cell costimulation by the phosphoinositide 3‐kinase inhibitor wortmannin
Authors: Ward Stephen G. , Wilson Anne , Turner Lynn , Westwick John , Sansom David M. 
Published: March 2007

AbstractT lymphocyte activation requires at least two signals, one via the antigen‐specific T cell receptor and a second via the surface molecule CD28 which provides signals critical to interleukin‐2 (IL‐2) production and T cell proliferation. We have previously shown (Ward S. G., Westwick J., Hall N. and Sansom D. M. Eur. J. Immunol. 1993. 23: 2572) that CD28 stimulates phosphoinositide (PI) 3‐kinase activity, indicating that D‐3 phosphoinositides may act as mediators of CD28‐induced T cell costimulation. Here, we report that immunoprecipitation of CD28 molecules from Jurkat cells stimulated with the CD28‐ligand B7, results in a ligand‐dependent association of CD28 with PI 3‐kinase. This association correlates with the appearance of PI 3‐kinase enzymatic activity in CD28 immunoprecipitates and the formation of D‐3 phosphoinositides. Consistent with the hypothesis that D‐3 phosphoinositides are important mediators of CD28 signaling, treatment of T cells with the PI 3‐kinase inhibitor wortmannin, inhibited both T cell proliferation and production of IL‐2, but not the response of T cells to exogenous IL‐2. Hence, abrogation of PI 3‐kinase activity by wortmannin, appears sufficient to disrupt the costimulatory pathway utilized by CD28, indicating a central role for this enzyme in the CD28 signaling pathway.
Studies on the interdependence of gp39 and B7 expression and function during antigen‐specific immune responses
Authors: Roy Meenakshi , Aruffo Alejandro , Ledbetter Jeffrey , Linsley Peter , Kehry Marilyn , Noelle Randolph 
Published: March 2007

AbstractInteractions between T and B cells are dynamic and regulated by interacting receptor: co‐receptors. Interactions between CD40 and its ligand, gp39, and the CD28/CTLA‐4 and B7 family members play a decisive role in regulating the progression of cognate interactions. The interdependence of gp39‐CD40 and CD28/CTLA‐B7 expression and function was studied in vitro during an antigeninduced immune response using T cells from mice expressing a transgenic T cell receptor (TCR). gp39 was induced on pigeon cytochrome c (PCC)‐transgenic T cells in the presence of antigen and antigen‐presenting cells. The antigen‐induced expression of gp39 on transgenic T cells was inhibited by antibodies to class II major histocompatibility complex, CD4 and LFA‐1, but not by CTLA‐4 Ig, anti‐B7‐1 or anti‐B7‐2. These data established that the antigen‐induced expression of gp39 was not dependent on co‐stimulation via CD28/CTLA‐4. The addition of PCC also resulted in the modest expression of B7‐1 and a more robust expression of B7‐2 on the cognate B cells. The addition of anti‐gp39 blocked the up‐regulated expression of B7‐1 and partially blocked the up‐regulated expression of B7‐2. The addition of anti‐gp39 and anti‐interleukin‐4 inhibited antigen‐induced expression of B7‐2 on B cells to near background levels. Studies on the up‐regulation of B7‐1 and B7‐2 on resting B cells showed that soluble gp39 up‐regulated B7‐1 and B7‐2 expression on B cells. In addition, interleukin‐4 and interferon‐γ up‐regulated B7‐2 expression on B cells. Taken together, these data demonstrate that the antigen‐induced expression of gp39 is dependent on TCR‐derived signals, yet independent of CD28/CTLA‐4 co‐stimulatory signals. Cognate interactions also resulted in the modest enhancement of B7‐1 expression and a more profound expression of B7‐2 which were completely or partially dependent on gp39‐CD40 interactions.
Soluble lipopolysaccharide receptor (CD14) is released via two different mechanisms from human monocytes and CD14 transfectants
Authors: Bufler Philip , Stiegler Gabor , Schuchmann Marcus , Hess Sigrun , Krüger Christian , Stelter Felix , Eckerskorn Christoph , Schütt Christine , Engelmann Hartmut 
Published: March 2007

AbstractThe receptor for lipopolysaccharide LPS (CD14) exists in a membrane‐associated (mCD14) and a soluble form (sCD14). Previous studies indicate that monocytes produce sCD14 by limited proteolysis of the membrane‐bound receptor. In this study we demonstrate that human monocytes also produce sCD14 by a protease‐independent mechanism. To investigate the molecular nature of this second pathway we studied sCD14 formation in the monocytic cell line Mono Mac 6 (MM6) and in CD14 transfectants. Both MM6 and the CD14 transfectants constitutively produce sCD14 by a protease‐independent mechanism. Structural analysis of sCD14 produced by the CD14 transfectants reconfirmed the presence of the COOH terminus predicted from the cDNA. Since glycosylphosphatidyl‐inositol anchor attachment is associated with the removal of a hydrophobic C‐terminal signal peptide, our finding demonstrates that the transfectants secrete sCD14 which escaped this posttranslational modification. Identical results obtained for sCD14 derived from peritoneal dialysis fluid of a patient with kidney dysfunction show the in vivo relevance of this pathway for sCD14 production.
Encephalitogenic, myelin basic protein‐specific T cells from naive rat thymus: preferential use of the T cell receptor gene Vβ8.2 and expression of the CD4− CD8− phenotype
Authors: Lannes‐Vieira Joseli , Goudable Bernard , Drexler Klaus , Gehrmann Jochen , Torres‐Nagel Nora , Hünig Thomas , Wekerle Hartmut 
Published: March 2007

AbstractUsing a primary limiting dilution approach to generate T cell lines, we compared myelin basic protein (MBP)‐specific T cell clones from naive unprimed Lewis rat thymuses with the corresponding T cell repertoire of primed rats. We found that in the naive thymus repertoire MBP‐specific, encephalitogenic T cell clones preferentially use T cell receptor Vβ8.2 genes, along with CDR3 sequences typical for the primed Lewis anti‐MBP response. In contrast to T cells from primed immune organs, which all display the CD4+ CD8− phenotype, the majority of naive thymus‐derived T cell clones expressed reduced levels of the CD4 co‐receptor. Some clones were completely CD4−CD8−, while others included CD4− CD8− subpopulations along with CD4+CD8− T cells. In the one mixed population examined in detail, the CD4−CD8− and CD4+CD8− T cell subpopulations used a T cell receptor with identical β chain sequence. The data suggest that in the Lewis rat the biased T cell receptor gene usage by encephalitogenic T cells is a property of the natural thymic T cell repertoire, possibly as a consequence of positive selection. The unusually low expression of CD4 in the major histocompatibility complex class II‐restricted autoreactive T cells could be related to their escape from negative selection within the thymus.
Antibodies that activate β2 integrins can generate different ligand binding states
Authors: Ortlepp Susan , Stephens Paul E. , Hogg Nancy , Figdor Carl G. , Robinson Martyn K. 
Published: March 2007

AbstractA human erythroleukemic cell line (K562) that does not normally express β2 integrins has been transfected with the genes encoding these integrins. The resulting cell lines show minimal background adhesion but can be stimulated to bind to appropriate substrates when activated with either of two different antibodies to CD18. The two antibodies appear to generate different ligand binding states in LFA‐1 such that different members of the ICAM family are recognized. Antibody‐activated complement receptor type 3 and p150,95‐transfected cells bind protein‐coated surfaces, although they require slightly different activation conditions for optimal binding.