bluuebunny/crossref_metadata_2025_split huggingface dataset:
Vascular endothelial growth factor rescues 2,3,7,8‐tetrachlorodibenzo‐p‐dioxin inhibition of coronary vasculogenesis
Authors: Ivnitski‐Steele Irena D. , Walker Mary K. 
Published: July 2003

AbstractBACKGROUNDWe previously demonstrated that the environmental pollutant 2,3,7,8‐tetrachlorodibenzo‐p‐dioxin (TCDD) reduces coronary vascular development in chick embryos in vivo. In the current study, we assessed whether TCDD inhibits early events in coronary endothelial tube formation and outgrowth, and whether this inhibition occurs through a vascular endothelial growth factor (VEGF)‐dependent mechanism.METHODSFertile chicken eggs were treated with control (corn oil) or TCDD (0.3 pmol TCDD/g) on incubation day 0. On embryonic day 6, cardiac ventricle explants were cultured on a three‐dimensional collagen gel, when coronary angioblasts are present, but prior to their assembly into endothelial tubes. Endothelial cells migrating out from explants were identified by immunohistochemistry, and endothelial tube number and length were quantitated. In addition, on incubation days 6 and 8, cardiac VEGF mRNA and protein were measured by reverse transcriptase‐polymerase chain reaction (RT‐PCR) and enzyme‐linked immunosorbent assay (ELISA), respectively.RESULTSEndothelial tube length and number were significantly reduced (40% ± 1.7% and 36% ± 3%, respectively) in TCDD explants, compared to controls. Recombinant exogenous VEGF, as well as hypoxic stimulation with CoCl2 or 10% O2, significantly increased the length and number of outgrowing tubes in TCDD cultures, and this stimulation was prevented by a VEGF neutralizing antibody. In contrast, VEGF neutralizing antibody reduced the length and number of tubes only in control cultures, and had no inhibitory effect on tube outgrowth from TCDD explants. Finally, hearts from TCDD‐treated embryos exhibited a significant reduction in both VEGF mRNA and protein, compared to controls.CONCLUSIONSThese data suggest that TCDD inhibits early coronary vascular outgrowth via a VEGF‐dependent mechanism. Birth Defects Research (Part A) 67:496–503, 2003. © 2003 Wiley‐Liss, Inc.
Using IPEDS to Develop a Classification System for Two‐Year Postsecondary Institutions
Authors: Merisotis Jamie P. , Shedd Jessica M. 
Published: July 2003

AbstractThis chapter explores the development of a classification system for two‐year institutions that can provide a framework for analysis and contribute to the discourse in public policy. The proposed classification system is based on cluster analyses using data from the National Center for Education Statistics' Integrated Postsecondary Education Data System (IPEDS).
On Markets and Other Matters: A Price Model for Public Two‐Year Colleges
Authors: Shaman Susan M. , Zemsky Robert 
Published: July 2003

AbstractCommunity colleges are often thought to constitute a separate sphere in higher education, one that is unique and largely self‐contained. This chapter calls into question that basic assumption, demonstrating that the price an individual community college charges is a function of the role and place that the institution occupies in the overall market for postsecondary education. The analysis suggests a classification that distinguishes colleges with respect to their emphasis on formal degree programs versus delivery of courses.
A Researcher's Perspective
Authors: Bailey Thomas R. 
Published: July 2003

AbstractThe diversity of community colleges justifies a more subtle system of categorization than the traditional Carnegie system, but the large number of missions taken on by community colleges complicates this goal. Any system must be based on a clear understanding of the goals of the categorization. This chapter makes a distinction between a characteristics‐based system and an output‐based system and uses that distinction to discuss the proposed classification schemes.
Caspase‐dependent and ‐independent apoptosis of mast cells induced by withdrawal of IL‐3 is prevented by Toll‐like receptor 4‐mediated lipopolysaccharide stimulation
Authors: Yoshikawa Hideshi , Tasaka Kachio 
Published: July 2003

AbstractIL‐3‐dependent mucosal‐like mast cells undergo apoptosis upon withdrawal of IL‐3. Generally, the apoptosis is mediated by the activation of caspases and inhibited by addition of the pan‐caspase inhibitors z‐VAD‐FMK or BOC‐D‐FMK. However, DNA fragmentation, a typical characteristic of apoptosis, is not inhibited by z‐VAD‐FMK or BOC‐D‐FMK in mast cell apoptosis. In this study, we demonstrate that the apoptosis of mast cells is mediated by both caspase‐dependent and ‐independent mechanisms. The caspase‐independent apoptosis is mediated by the translocation of endonuclease G from mitochondria into nuclei. Withdrawal of IL‐3 caused down‐regulation of Bcl‐xL, resulting in a drop in mitochondrial membrane transition potential followed by the release of cytochrome c and endonuclease G from mitochondria. However, stimulation of mast cells through Toll‐like receptor 4 (TLR4) by lipopolysaccharide prevented mast cell apoptosis by inducing expression of Bcl‐xL. Moreover, the activation of mast cells by LPS is enhanced in the presence of IFN‐γ, which up‐regulates the expression of cell surface TLR4. Taken together, these observations provide evidence that mast cells play importantroles not only in allergic reactions but also in innate immunity recognizing enterobacteria through TLR4, and are regulated differently from allergic inflammation by Th1 cytokines.
Reduced transforming growth factor‐β1‐producing T cells in the duodenal mucosa of children with food allergy
Authors: Pérez‐Machado Miguel A. , Ashwood Paul , Thomson Michael A. , Latcham Frances , Sim Rosalind , Walker‐Smith John A. , Murch Simon H. 
Published: July 2003

AbstractInfant food allergies are increasing, and many breast‐fed infants now sensitize to maternally‐ingested antigens. As low‐dose oral tolerance requires generation of suppressor lymphocytes producing TGF‐β1 (Th3 cells), we studied these cells in duodenal biopsies after diagnostic endoscopy. Spontaneous production of Th1, Th2 and Th3 cytokines by duodenal lymphocytes was studied using flow cytometry in 20 children with no eventual clinico‐pathological diagnosis (controls), 30 children with multiple food allergy, nine with celiac disease and six with inflammatory enteropathies. Immunohistochemistry and in situ hybridization were used to localize TGF‐β1 protein and mRNA in matched biopsies. We found no significant Th1/Th2 skewing amongst mucosal lymphocytes in allergic children compared to controls, although celiac and inflammatory enteropathy patients showed increased Th1 responses. By contrast, the allergic children showed reduction of TGF‐β1+ lymphocytes in both epithelial and lamina propria compartments. Reduction of TGF‐β1 expression was also seen in mononuclear cells and epithelium in food allergy by immunohistochemistry and in situ hybridization. The dominant mucosal abnormality in food allergic children was, thus, not Th2 deviation but impaired generation of Th3 cells. As generation of these cells requires innate immune response to enteric bacteria, we suggest that changing infectious exposures may inhibit primary establishment of basic oral tolerance mechanisms.
Human NK cells express Fc receptors for IgA which mediate signal transduction and target cell killing
Authors: Mota Gabriela , Manciulea Mioara , Cosma Ecaterina , Popescu Iulia , Hirt Mirela , Jensen‐Jarolim Erika , Calugaru Ana , Galatiuc Cecilia , Regalia Teodor , Tamandl Dietmar , Spittler Andreas , Boltz‐Nitulescu George 
Published: July 2003

AbstractReceptors for the Fc region of IgG (FcγRIIIa, FcγRIIc) and IgM (FcμR) were previously described on NK cells. In this work the expression of Fc receptors for IgA (FcαR) on humanNK cells and the signaling events were investigated. The FcαR was demonstrated by flow cytometry using secretory IgA (sIgA) and anti‐human IgA antibody. The percentage of NK cells (CD3–CD56+CD16+) expressing FcαR ranged between 55.7% and 95.7%, with a mean ± SD of 75.2±11.8. The association constant and the number of 125I‐labeled sIgA (125I‐sIgA) molecules bound per cell, calculated by Scatchard analysis, were 2×107 M–1 and 1.7×104, respectively. The binding specificity was proved by inhibition experiments. Cold sIgA but not IgA Fab fragments were able to inhibit 125I‐sIgA binding in a concentration‐dependent manner. Binding of sIgA to NK cells was neither inhibited by anti‐mannose receptor antibody, nor by L‐fucose, D‐galactose, D‐glucose, D‐mannose or N‐acetyl‐D‐glucosamine. Pretreatment of NK cells with polymeric IgA inhibited their capacity to kill 51Cr‐labeled K562 target cells by 34.8%, whereas with monomeric IgA only by 13.1%. Ligand‐induced clustering of the FcαR resulted in activation of tyrosine kinases Lck, Syk and phosphatidylinositol 3‐kinase. The present studies support the concept that human NK cells bind preferentially sIgA and polymeric IgA with moderate affinity via FcαR, which is different from the FcαRI/CD89 and other carbohydrate‐recognizing receptors like mannose receptor/CD206. This novel structure mediates signal transduction and cell killing.
ME3738 protects from concanavalin A‐induced liver failure via an IL‐6‐dependent mechanism
Authors: Klein Christian , Wüstefeld Torsten , Heinrich Peter C. , Streetz Konrad L. , Manns Michael P. , Trautwein Christian 
Published: July 2003

AbstractME3738 is a new compound that attenuates liver disease in several models of acute and chronic liver inflammation. We used the concanavalin A (Con A) model to elucidate the molecular mechanismsof ME3738 to block liver cell damage. Pretreatment of BALB/c mice with ME3738 prior to Con A injection resulted in a significant reduction in liver injury. The protective effect of ME3738 prior to Con A injection was associated with a reduction in IL‐6 serum levels and NF‐κB DNA binding in liver nuclear extracts. However, STAT3 DNA binding was induced via ME3738 prior to Con A injection. Further analysis showed that ME3738 induces IL‐6 serum levels and activates STAT3 DNA binding and target gene transcription. The relevance of this finding was assessed in IL‐6–/– mice. Inthese animals, ME3738 induced no increase in IL‐6 serum expression, and activation of IL‐6‐dependent pathways was not found. In addition, ME3738 did not protect IL‐6–/– animals from Con A‐induced liver failure, while IL‐6 injection was still effective. Therefore, we demonstrate that ME3738 triggers IL‐6 expression, which activates pathways that are relevant to protect from Con A‐induced liver failure.
Vav exchange factor counteracts the HIV‐1 Nef‐mediated decrease of plasma membrane GM1 and NF‐AT activity in T cells
Authors: Tuosto Loretta , Marinari Barbara , Andreotti Mauro , Federico Maurizio , Piccolella Enza 
Published: July 2003

AbstractSeveral findings support the importance of GM1‐enriched lipid microdomains of plasma membrane and of Vav, an essential regulator of actin cytoskeletal rearrangement, in the regulation of T cell activation. Moreover, a functional link among lipid microdomains, Vav and the HIV product Nef has been described. These observations suggest that Nef can modify plasma membrane GM1, affecting the behavior of HIV‐infected cells towards antigen recognition and Vav towards counteracting such an effect. We observed that Nef expression, either following viral infection or ectopic expression, significantly decreased the level of plasma membrane GM1 in unstimulated T cells. This down‐regulation was associated with the inhibition of NF‐AT activation, but not with NF‐κB activation inducedby TCR engagement. Dissecting the signaling pathway that regulates NF‐AT activation, we found that Nef inhibited exclusively the Ca2+/calcineurin cascade, whereas the JNK cascade and AP‐1 transcriptional activity were not affected. Our evidence that Vav overexpression counteracted both the Nef‐induced decrease of GM1 expression and the inhibition of NF‐AT activity, suggests a novel mechanism by which Nef may interfere with TCR‐mediated activation through the modulation of intracellular trafficking and clustering of GM1‐enriched microdomains at the cell surface.
Lysophosphatidic acid induces human natural killer cell chemotaxis and intracellular calcium mobilization
Authors: Jin Yixin , Knudsen Eirunn , Wang Ling , Maghazachi Azzam A. 
Published: July 2003

AbstractWe have investigated the effects of the bioactive lipid lysophosphatidic acid (LPA) on several functions of activated human natural killer (NK) cells. Flow cytometric and immunoblot analyses show that these cells express LPA1, LPA2 and LPA3. LPA but not its precursor phosphatidic acid (PA) induces the chemotaxis of NK cells, an activity that is inhibited by prior treatment of the cells with pertussis toxin (PTX). In addition, LPA induces the mobilization of intracellular calcium, an effect that is markedly inhibited by PTX, but is not inhibited by the addition of EGTA. PA also induces calcium flux in NK cells, but with much lower efficacy than LPA. Cross‐desensitization experiments demonstrate that LPA and PA utilize different receptors. Moreover, LPA or PA but not sphingosine 1‐phosphate, enhances IFN‐γ secretion by activated NK cells. Our results may shed some light on the findings that activated NK cells are found at the sites of tumor growth.
Sensitivity of IL‐5 production to the cAMP‐dependent pathway in human T cells is reduced by exogenous IL‐2 in a phosphoinositide 3‐kinase‐dependent way
Authors: Heijink Irene H. , Kauffman Henk F. , Postma Dirkje S. , de Monchy Jan G. R. , Vellenga Edo 
Published: July 2003

AbstractThe cAMP‐dependent pathway plays an important role in the regulation of T cell‐mediated immune responses by inhibition of T cell proliferation, activation and production of Th1‐like cytokines.Depending on costimulatory signals and on the activation status of T cells, cAMP also regulates the production of Th2‐like cytokines, yet the mechanism is not completely defined. We investigated the effect of costimulation with IL‐2 on cAMP‐mediated inhibition of IL‐5 secretion and the signaling pathways involved in these effects in freshly isolated, α‐CD3/α‐CD28‐stimulated human T lymphocytes. We demonstrate that IL‐2 counteracts the cAMP‐mediated inhibitory effects on IL‐5 secretion by the modulation of phosphoinositide 3‐kinase (PI3‐K)‐dependent signaling. Our results indicate that phosphorylation of cAMP‐responsive element‐binding protein (CREB) and the activity of the small GTPase Rap1 are unlikely involved in the protective effect of IL‐2. Instead, the effect of IL‐2may be mediated by the PI3‐K‐dependent inactivation of the forkhead‐related transcription factor FKHR‐L1, down‐regulation of p27kip and abrogation of the cAMP‐mediated inhibition of activator protein (AP)‐1 binding activity. Together, our results indicate that increased IL‐2‐dependent PI3‐K signaling leads to impaired negative feedback control of the production of Th2‐type cytokine IL‐5 by the cAMP‐dependent pathway.
Essential pathogenic role of endogenous IL‐18 in murine diabetes induced by multiple low doses of streptozotocin. Prevention of hyperglycemia and insulitis by a recombinant IL‐18‐binding protein: Fc construct
Authors: Nicoletti Ferdinando , Marco Roberto Di , Papaccio Gianpaolo , Conget Ignacio , Gomis Ramon , Bernardini Renato , Sims John E. , Shoenfeld Yehuda , Bendtzen Klaus 
Published: July 2003

AbstractIL‐18 is a cytokine structurally and functionally related to IL‐1 that, in synergy with IL‐12, stimulates the synthesis of IFN‐γ from T lymphocytes and natural killer cells. Because IFN‐γ plays a key pathogenic role in the development of murine immunoinflammatory diabetes induced by multiple low doses of streptozotocin (STZ) we investigated the effect of negating the actions of endogenous IL‐18 in this model by administering recombinant IL‐18‐binding protein:Fc (IL‐18 bp:Fc). C57BL/6 mice were injected once daily with 40 mg/kg STZ for 5 consecutive days, day 0 being the first day of STZ challenge. Relative to control animals treated in parallel with either PBS or human IgG, mice treated from day –3 to day 7 with daily doses of 150 μg of IL‐18 bp:Fc exhibited lowerincidence of diabetes and milder insulitis. In contrast, mice that were treated with IL‐18 bp:Fc from day 7 to day 14 exhibited clinical and histological signs of STZ‐induced diabetes similar to those of control mice treated with IgG. The protective effect of IL‐18 bp:Fc was accompanied by modified ex vivo immune responses, in that spleen cells and peritoneal macrophages contained fewer IFN‐γ secreting cells and released lower amounts of nitrite (an index of nitric oxide production) and IL‐1β. We conclude that intact IL‐18 function is essential for the full diabetogenic effectof low dose STZ in C57BL/6 mice.
TEA regulates local TCR‐Jα accessibility through histone acetylation
Authors: Mauvieux Laurent , Villey Isabelle , de Villartay Jean‐Pierre 
Published: July 2003

AbstractEnhancer α‐dependent histone acetylation has been proposed as a molecular mechanism underlying the control of accessibility of recombination signal sequences along the TCRα locus. Herewe show that chromatin acetylation along the first Jα segments is under the dependence of the T early α element (TEA), located upstream of TCRJα locus. The targeted deletion of TEA leads to an absence of histones H3 and H4 tail acetylation, while maintaining histone acetylation in the region spanning downstream Jα segments. During thymocyte maturation, TEA‐dependent histone acetylation appears at immature single‐positive stage, known to represent the stage of VαJα initiation. TEA‐dependent histone acetylation of the most upstream Jα segments leads to enhancedDNA accessibility thus optimizing TCRJα usage and increasing Ag receptor diversity potential.
Oxidative‐stress‐induced T lymphocyte hyporesponsiveness is caused by structural modification rather than proteasomal degradation of crucial TCR signaling molecules
Authors: Cemerski Saso , van Meerwijk Joost P. M. , Romagnoli Paola 
Published: July 2003

AbstractIn several human pathologies (e.g. cancer, rheumatoid arthritis, AIDS and leprosy) oxidative stress induces T cell hyporesponsiveness. Hyporesponsive T cells often appear to display impaired expression of some (e.g. TCR‐ζ, p56lck and LAT) but not all (e.g. TCR‐αβ and CD3‐ϵ) crucial TCR‐proximal signaling molecules but the underlying mechanisms have as yet not been identified. Using an in vitro system for oxidative‐stress‐induced T cell hyporesponsiveness we here report two sequential effects of oxidative stress on TCR signaling molecules: protein alterations and proteasomal degradation. We have identified the C‐terminal part of TCR‐ζ and the membrane‐proximal domain of p56lck as potential targets for modifications induced by reactive oxygen species. Oxidative‐stress‐exposed proteins were differentially susceptible to proteasomal degradation: whereas modified TCR‐ζ was relatively resistant, reactive oxygen species (ROS)‐altered LAT and p56lck were much more susceptible. Importantly, we found that T cell hyporesponsiveness best correlated with ROS‐dependent protein alteration since inhibition of proteasomal degradation did not restore function. Finally, our data provide an explanation for the paradox of reduced TCR‐ζ signals combined with unaltered TCR‐αβ and CD3‐ϵexpression levels: the TCR‐ζ chain in hyporesponsive T cells is still expressed but no longer detectable by certain mAb recognizing ROS‐sensitive epitopes.
CRP‐ductin, the mouse homologue of gp‐340/deleted in malignant brain tumors 1 (DMBT1), binds gram‐positive and gram‐negative bacteria and interacts with lung surfactant protein D
Authors: Madsen Jens , Tornøe Ida , Nielsen Ole , Lausen Mette , Krebs Inge , Mollenhauer Jan , Kollender Gaby , Poustka Annemarie , Skjødt Karsten , Holmskov Uffe 
Published: July 2003

AbstractCRP‐ductin is a protein expressed mainly by mucosal epithelial cells in the mouse. Sequence homologies indicate that CRP‐ductin is the mouse homologue of human gp‐340, a glycoprotein that agglutinates microorganisms and binds the lung mucosal collectin surfactant protein‐D (SP‐D). Here we report that purified CRP‐ductin binds human SP‐D in a calcium‐dependent manner and that the binding is not inhibited by maltose. The same properties have previously been observed for gp‐340 binding of SP‐D. CRP‐ductin also showed calcium‐dependent binding to both gram‐positive and ‐negative bacteria. A polyclonal antibody raised against gp‐340 reacted specifically with CRP‐ductin in Western blots. Immunoreactivity to CRP‐ductin was found in the exocrine pancreas, in epithelial cells throughout the gastrointestinal tract and in the parotid ducts. A panel of RNA preparations from mouse tissues was screened for CRP‐ductin and SP‐D expression by reverse transcription‐PCR. The pancreas was the main site of synthesis of CRP‐ductin, but transcripts were also readily amplified from salivary gland, the gastrointestinal tract, liver, testis, uterus and lung. Lung was the main site of synthesis of SP‐D, but transcripts were also amplified from uterus, salivary gland, thymus, thyroid gland, pancreas and testis. We conclude that CRP‐ductin is the mouse homologue of human gp‐340 and that its capacity to bind SP‐D as well as gram‐negative and gram‐positive bacteria suggests a role in mucosal immune defense.
Oxidative stress stimulates IL‐4 and IL‐6 production in mast cells by an APE/Ref‐1‐dependent pathway
Authors: Frossi Barbara , De Carli Marco , Daniel Kenn Curt , Rivera Juan , Pucillo Carlo 
Published: July 2003

AbstractMast cells are exposed to an oxidative environment in the course of allergic and inflammatory reactions. We have examined the effects of H2O2 stimulation in a primary rat basophilic leukemia cell line (RBL‐2H3) and compared with IgE‐dependent stimulation. Like IgE stimulation, H2O2 up‐regulates IL‐4 and IL‐6 gene expression and cytokine secretion, shows a little effect on IL‐5 but does not induce IL‐10 gene expression. Simultaneous H2O2 treatment and FcϵRI triggering of mast cells has additive effects on IL‐4 expression. In addition, we show that both stimuli induce the nuclear translocation of APE/Ref‐1, a bifunctional enzyme that stimulates the DNA‐binding activity of several transcription factors through the reduction of highly reactive cysteines. Conditional inactivation of APE/Ref‐1 expression abolishes H2O2‐induced IL‐4 and IL‐6 gene expression but does not affect that induced by FcϵRI stimulation. Our findings indicate that oxidative stress activates the gene expression of a specific cytokine pattern in mast cells through an APE/Ref‐1‐dependent pathway, which is distinct from theone that is activated by FcϵRI stimulation. Nonetheless, H2O2 and FcϵRI signalings are additive in augmenting IL‐4 production. Most importantly, oxidative stress can induce a pro‐type 2 inflammatory response from mast cells that is independent of FcϵRI stimulation.
4‐1BB enhances CD8+ T cell expansion by regulating cell cycle progression through changes in expression of cyclins D and E and cyclin‐dependent kinase inhibitor p27kip1
Authors: Lee Hyeon‐Woo , Nam Kyung‐Ok , Park Su‐Jung , Kwon Byoung S. 
Published: July 2003

AbstractThe T cell costimulatory receptor 4‐1BB enhances cell cycle progression and proliferation of CD8+ T cells in both an IL‐2‐dependent and ‐independent manner. In these studies, 4‐1BB costimulation was shown to increase cyclin D2, D3, and E expression, and concomitantly down‐regulate the expression of the cyclin‐dependent kinase inhibitor p27kip1. 4‐1BB increases cyclin D2 transcription via mitogen‐activated/extracellular signal‐regulated kinase‐1/2 and LY294002‐sensitive phosphatidylinositol 3‐kinase (PI3K) signaling pathways. In addition, 4‐1BB up‐regulates cyclin D2 translation via PI3K/Akt/mammalian target of rapamycin (mTOR) pathways, presumably triggered by IL‐2/IL‐2 receptor ligation. The enhanced cyclin D2 and D3 expression initiates up‐regulation of cyclin E expression and down‐regulation of p27kip1. Our results suggest a role for cyclin D2, D3, and E, and p27kip1 proteins in the 4‐1BB‐mediated cell cycle progression of CD8+ T cells in vivo.