bluuebunny/crossref_metadata_2025_split huggingface dataset:
A comparative study of adults with and without self‐reported learning disabilities in six English‐speaking populations: What have we learned?
Authors: Vogel Susan A. , Holt Janet K. 
Published: October 2003

AbstractThe purpose of this study was to compare adults with and without self‐reported learning disabilities (SRLD and NSRLD) from six English‐speaking populations including: English‐speaking Canada, Great Britain, The Republic of Ireland, New Zealand, Northern Ireland, and the United States. These six populations were selected because they were all English‐speaking populations, participated in the first administration of the International Adult Literacy Survey (IALS), and included the optional questions regarding the presence of a disability. In this study, we compared the groups on prevalence by population, percentage of each group by age and gender, awareness of learning disabilities and problems in school, document and quantitative literacy proficiency, educational attainment, reasons for dropping out of school, and employment, occupational and financial status. Findings were reported among these six populations within an historical perspective including differences in awareness and definition of learning disabilities, public policy, special education services, reading pedagogy, and teacher preparation. Recommendations are made for improving literacy and long‐term outcomes for those with learning disabilities in all nations as well as future research directions. Copyright © 2003 John Wiley & Sons, Ltd.
Endothelial cell cytoprotection induced in vitro by allo‐ or xenoreactive antibodies is mediated by signaling through adenosine A2 receptors
Authors: Delikouras Alexandros , Fairbanks Lynette D. , Simmonds Anne H. , Lechler Robert I. , Dorling Anthony 
Published: October 2003

AbstractEndothelial cell (EC) expression of proteins such as hemoxygenase‐1 or Bcl‐xL is associated with enhanced survival of vascularized allo‐ or xenografts. These grafts are resistant to humoral rejection, a phenomenon called accommodation. In vitro, low concentrations of allo‐ and xenoreactive antibody (XNA) induce a cytoprotective phenotype in EC similar to that seen in accommodated grafts. In this study we examine whether adenosine plays a role in antibody‐induced cytoprotection. Porcine EC were incubated with human anti‐pig XNA or specific alloantibody. EC expressed Bcl‐xL and were protected from TNF‐mediated apoptosis. Bcl‐xL expression was inhibited by an adenosine A2 receptor antagonist. Human anti‐pig XNA were shown to bind and induce cyclic adenosine 3′,5′‐monophosphate (cAMP) generation through these receptors. This activity was abolished by depletion of anti‐galα(1–3)gal‐specific XNA. In contrast, alloantibody caused adenosine production. Protection from TNF‐mediated apoptosis was also mediated through A2 receptor but involved additional non‐cAMP‐dependent signaling. This study indicates a molecular mechanism common to both antibody‐mediated cytoprotection and ischemic preconditioning and suggests a potential therapeutic avenue based on adenosine for improving the outcome of transplanted grafts in those patients with pre‐existing anti‐graft antibody.
The brain as an immune privileged site: dendritic cells of the central nervous system inhibit T cell activation
Authors: Suter Tobias , Biollaz Gregoire , Gatto Dominique , Bernasconi Luca , Herren Tobias , Reith Walter , Fontana Adriano 
Published: October 2003

AbstractDendritic cells (DC) are unique in their ability to prime naive T cells and initiate adaptive immunity. In recent years, DC were identified in the inflamed central nervous system (CNS), but their role in the initiation or regulation of the tissue specific immune response is unknown. As shown here, DC isolated from mice with experimental autoimmune encephalomyelitis (EAE) exhibit a maturational phenotype similar to immature bone marrow‐derived DC or splenic DC as characterized by intermediate surface MHC class II and low expression of the costimulatory molecule CD80. However, they are unable to prime naive T cells. Moreover, they inhibit T cell proliferation stimulated by mature bone marrow‐derived DC. TGFβ, IL‐10 and TRAIL were found to significantly contribute to the CNS‐DC‐mediated inhibition of allo‐T cell proliferation. Thus CNS‐DC may be the key responsibles for maintaining immune privilege within the inflamed CNS.
Intrapulmonary targeting of RANTES/CCL5‐responsive cells prevents chronic fungal asthma
Authors: Schuh Jane M. , Blease Kate , Brühl Hilke , Mack Matthias , Hogaboam Cory M. 
Published: October 2003

AbstractRegulated upon activation in normal T cells, expressed, and secreted (RANTES)/CCL5 is abundantly expressed during atopic asthma, suggesting that it is an important mediator of this disease. The contribution of intrapulmonary RANTES/CCL5‐sensitive cells during Aspergillus fumigatus‐induced airway disease in mice was assessed in this study. The intranasal delivery of a chimeric protein comprised of RANTES/CCL5 and a truncated version of Pseudomonas exotoxin A (RANTES‐PE38) significantly attenuated serum IgE, peribronchial eosinophilia, and airway hyperreactivity when it was administered from day 0 to 15 after intratracheal conidia challenge in A. fumigatus‐sensitized mice but had little effect when delivered from day 15 to 30 after conidia challenge. Intranasal RANTES‐PE38 treatment enhanced macrophage recruitment and accelerated fungal clearance in the lungs of RANTES‐PE38‐treated mice. These data reveal a major role for RANTES/CCL5 and its receptors in the development of fungal asthma yet reveal only a modest role in the chronic remodeling of the allergic airway in this disease.
The cyclin‐dependent kinase inhibitors p27Kip1 and p21Cip1 are not essential in T cell anergy
Authors: Verdoodt Berlinda , Blazek Tino , Rauch Pia , Schuler Gerold , Steinkasserer Alexander , Lutz Manfred B. , Funk Jens Oliver 
Published: October 2003

AbstractRecent evidence suggests that the cyclin‐dependent kinase (Cdk) inhibitors p27Kip1 and p21Cip1 are important factors in T cell anergy, but it has remained unclear whether anergy can be induced in their absence. We therefore induced anergy by stimulation of purified T cells from wild‐type, p21Cip1–/–, and p27Kip1–/– mice with anti‐CD3 antibodies. Anergic wild‐type T cells were arrested in the G1 phase of the cell cycle with a high p27Kip1 protein level and low Cdk2 activity. In p27–/– and p21–/– T cells, the pattern of protein expression was preserved, but Cdk2 activity was increased. To confirm the in vivo relevance of these data, anergy was induced by repeated injection of mice with staphylococcal enterotoxin B (SEB), which leads to partial deletion of the responsive Vβ8+ T cell population and anergy in the remaining T cells. p21–/– mice and wild‐type mice reacted similarly tothis treatment. p27–/– mice showed reduced deletion of SEB‐responsive T cells, but persisting T cells were anergic. These data indicate that other cell cycle regulators contribute to the cell cycle arrest of anergic T cells, as neither Cdk inhibitor is required for the induction of anergy.
IFN‐γ production in human NK cells through the engagement of CD8 by soluble or surface HLA class I molecules
Authors: Spaggiari Grazia Maria , Contini Paola , Negrini Simone , Dondero Alessandra , Carosio Roberta , Ghio Massimo , Puppo Francesco , Indiveri Francesco , Zocchi Maria Raffaella , Poggi Alessandro 
Published: October 2003

AbstractThe engagement of CD8 on NK cell surface by either surface or soluble HLA class I (sHLA‐I) molecules induces synthesis and secretion of IFN‐γ. HLA‐I‐mediated effects were inhibited by the covering of CD8 with specific anti‐CD8 monoclonal antibodies, indicating a direct interaction of HLA‐I and CD8. That CD8 ligation induces IFN‐γ production was further supported by the finding that cross‐linking of CD8 led to release of IFN‐γ at similar levels to those obtained with HLA‐I. The sHLA‐I‐induced IFN‐γ production via CD8 was strongly down‐regulated by the engagement of the inhibitory isoforms of either CD94/NKG2 complex by sHLA‐I‐non‐(A,B,C,G) (putative sHLA‐E) or CD158b by sHLA‐I‐Cw3 allele. Ligation of CD8 did not elicit, different from other activating NK cell surface molecules such as CD16 or CD69, triggering of NK cell‐mediated cytolysis. Cyclosporin A, but not concanamycin A, an H+‐ATPase vacuolar inhibitor which affects perforin and granzyme release, strongly reduced the sHLA‐I‐mediated CD8‐dependent IFN‐γ production but did not affect cytolytic activity of NK cells, suggesting that different biochemical pathways are involved. Altogether, these findings indicate that CD8 engagement by sHLA‐I activates a cyclosporin A‐dependent pathway leading to production and secretion of IFN‐γ which may play a role in the regulation of innate immune responses in humans.
In vivo expression of recombinant pregnancy‐specific glycoprotein 1a induces alternative activation of monocytes and enhances Th2‐type immune response
Authors: Motrán Claudia C. , Diaz Fernando López , Montes Carolina L. , Bocco José Luis , Gruppi Adriana 
Published: October 2003

AbstractIt has been proposed that pregnancy‐specific factors could be responsible for shift the balance of cytokine profiles during maternal immune response from Th1‐type reactivity into a "less‐damaging" Th2‐type reactivity. In the present work, we investigated the in vivo function of human pregnancy‐specific glycoprotein (PSG)1a, the major variant of PSG polypeptides released into thecirculation during pregnancy, on the modulation of the innate and adaptive immune response. For this, BALB/c mice were injected with a vaccinia virus‐based vector harboring the human PSG1a cDNA (Vac‐PSG1a) 4 days before immunization with ovalbumin (OVA) in complete Freund's adjuvant, and the early specific T cell response against OVA was evaluated 8 days post‐immunization. We also studied the activation status of spleen and peritoneal monocytes/macrophages (Mo) populations from Vac‐PSG1a‐treated mice, and explored whether PSG1a‐targeted Mo could affect the Th‐type commitment by investigating their impact on the differentiation of naive T cells. Our data show that the treatment with Vac‐PSG1a is able to induce a state of alternative activation on Mo. Furthermore, the generation of the immune response in the context of these alternatively activated antigen‐presenting cells may shift T cell differentiation to Th2‐type immunity which is more compatible with a successful pregnancy.
T cell stimulation in the absence of exogenous antigen: a T cell signal is induced by both MHC‐dependent and ‐independent mechanisms
Authors: Bettini Matthew , Xi Hongkang , Kersh Gilbert J. 
Published: October 2003

AbstractMature T cells residing in peripheral lymphoid organs have frequent contact with antigen presenting cells (APC). Such contact may be required for T cell survival, but the degree to which signals in mature T cells are induced by TCR recognition of self peptide/MHC complexes is unclear. We have used induction of the early growth response gene 1 (Egr1) as an indicator of signal transductionin 3.L2 (I‐Ek‐restricted) T cells interacting with APC in the absence of exogenous antigen. The data show that Egr1 can be induced in 3.L2 T cells by TCR recognition of self peptides presented by I‐Ek. However, a more transient induction of Egr1 can be induced in 3.L2 T cells interacting with dendritic cells derived from class II/β2m double‐deficient mice. Egr1 inductionafter T cell‐APC contact was also observed in a freshly isolated polyclonal CD4 T cell population. The data suggest that self peptide/MHC recognition by the TCR induces a signal in T cells and that dendritic cells can also induce a more transient T cell signal by an MHC‐independent mechanism.
Macrophage colony‐stimulating factor‐dependent macrophage proliferation is mediated through a calcineurin‐independent but immunophilin‐dependent mechanism that mediates the activation of external regulated kinases
Authors: Comalada Monica , Valledor Annabel F. , Sanchez‐Tilló Ester , Umbert Ignacio , Xaus Jordi , Celada Antonio 
Published: October 2003

AbstractCalcineurin is constitutively expressed in bone marrow‐derived macrophages. However, macrophage response to macrophage colony‐stimulating factor (M‐CSF) was not impaired by the use of either calcineurin inhibitors (W‐13, chlorpromazine and trifluoperazine), calcium chelators (BAPTA‐AM) or Ca2+ channel antagonists (verapamil, nifedipine and diltiazem). Inhibition of calcineurin expression by inhibitory antisense RNA treatment did not result in an inhibition of M‐CSF‐dependent proliferation. Only very high doses of cyclosporin A and FK506 inhibited macrophage proliferation induced by growth factors, such as M‐CSF, granulocyte‐macrophage (GM)‐CSF or IL‐3. This inhibitory action is mediated by the peptidylprolyl isomerase activity of the immunophilins, as demonstrated bythe use of specific inhibitors (rapamycin and sanglifehrin A). These isomerase inhibitors exerted a negative effect on a key element involved in macrophage proliferation, namely the M‐CSF‐dependent activation of the extracellular signal‐regulated kinases (ERK). In summary, the data presented here provide new insights in the mechanism of macrophage proliferation, which may have relevant consequences. First, we showed that in M‐CSF‐dependent proliferation calcineurin is not involved, and second, that immunophilins play a key role and their activation blocks ERK activation.
Pituitary adenylate cyclase‐activating polypeptide inhibits cutaneous immune function
Authors: Kodali Sreedevi , Friedman Ilyse , Ding Wanhong , Seiffert Kristina , Wagner John A. , Granstein Richard D. 
Published: October 2003

AbstractEpidermal nerves are closely associated with Langerhans cells (LC) and may be able to release factors, such as calcitonin gene‐related peptide and epinephrine, that affect LC function. LC and the LC‐like cell line XS106 express mRNA for the pituitary adenylate cyclase‐activating polypeptide (PACAP) receptors VPAC1 and VPAC2. We examined whether PACAP regulates cutaneous immunity. Intradermal administration of PACAP prior to application of a contact sensitizer at the injected site inhibited the induction of contact hypersensitivity. Pretreatment of murine epidermal cells enriched for LC content (∼12% LC) with PACAP inhibited their ability to elicit delayed‐type hypersensitivity in previously immunized mice. In vitro, PACAP suppressed the ability of both murine epidermal cells and highly purified LC (∼95%) to present antigen to a T cell clone and hybridoma. Furthermore, in LC and the XS106 cell line, PACAP inhibited the
LPS/GM‐CSF‐induced stimulation of IL‐1β secretion and augmented IL‐10 production. PACAP also down‐regulated CD86 expression in LPS/GM‐CSF‐stimulated XS106 cells. The immunosuppressive effects of PACAP may be due to modulation ofcytokine production and CD86 expression.
Cholera toxin activates dendritic cells through dependence on GM1‐ganglioside which is mediated by NF‐κB translocation
Authors: Kawamura Yuki I. , Kawashima Rei , Shirai Yuko , Kato Rie , Hamabata Takashi , Yamamoto Masafumi , Furukawa Koichi , Fujihashi Kohtaro , McGhee Jerry R. , Hayashi Hideo , Dohi Taeko 
Published: October 2003

AbstractCholera toxin (CT) is a potent adjuvant; however, the mechanism for its ability to enhance mucosal immunity has not been fully elucidated. We report here that CT exerts its adjuvant propertiesby signaling through the GM1 ganglioside receptor. When ganglioside‐defective mice were given the antigen (Ag) ovalbumin (OVA) with CT by the oral route, CT failed to support either OVA‐specific antibody or CD4+ T cell responses. In vitro treatment of murine bone marrow‐derived dendritic cells (DC) with CT induced full maturation as evidenced by up‐regulation of the costimulatory molecules, as well as by an enhanced ability to effectively present OVA for Ag‐specific T cell responses. On the other hand, ganglioside‐defective DC failed to differentiate to full function as Ag‐presenting cells in response to CT. Since ganglioside‐defective DC showed a mature phenotype after stimulation with lipopolysaccharide (LPS), the effects of CT on DC was independent of signal transduction through adjuvant receptor for LPS, the Toll‐like receptor 4. Furthermore, CT also induced nuclear translocation of nuclear factor (NF)‐κB in DC in a GM1‐dependent fashion. These results highlight gangliosides expressed by DC for recognition of the non‐self protein bacterial enterotoxin, which employ a unique signaling pathway to induce both innate and adaptive immunity.
Microbial Toll‐like receptor ligands differentially regulate CXCL10/IP‐10 expression in fibroblasts and mononuclear leukocytes in synergy with IFN‐γ and provide a mechanism for enhanced synovial chemokine levels in septic arthritis
Authors: Proost Paul , Vynckier An‐Katrien , Mahieu Frank , Put Willy , Grillet Bernard , Struyf Sofie , Wuyts Anja , Opdenakker Ghislain , Damme Jo Van 
Published: October 2003

AbstractThe CXC chemokine IFN‐γ‐inducible protein‐10 (IP‐10/CXCL10) activates CXC chemokine receptor 3 (CXCR3) and attracts activated T cells and natural killer cells. Peripheral blood mononuclearcells (PBMC) produce low but significant amounts of IP‐10/CXCL10 protein upon stimulation with double‐stranded (ds) RNA, the Toll‐like receptor 3 (TLR3) ligand. IFN‐γ is a superior IP‐10/CXCL10inducer. The bacterial TLR4 and TLR2 ligands, LPS and peptidoglycan (PGN), inhibit IFN‐γ‐ or dsRNA‐dependent IP‐10/CXCL10 production in PBMC, whereas IL‐8/CXCL8 production was enhanced. In fibroblasts a different picture emerges with IFN‐γ inducing moderate and dsRNA provoking strong IP‐10/CXCL10 production. Furthermore, treatment of fibroblasts with IFN‐γ in combination with bacterial LPS or PGN results in a synergistic production of IP‐10/CXCL10 and IL‐8/CXCL8. The synergistic induction of IP‐10/CXCL10 in fibroblasts is reflected by significantly enhanced IP‐10/CXCL10 concentrations in synovial fluids of septic compared to osteoarthritis patients to reach on average higher levels than those of IL‐8/CXCL8. These high amounts of IP‐10/CXCL10 produced by connective tissue fibroblasts not only attract CXCR3 expressing activated Th1 cells and natural killer cells to sites of infection but may also antagonize the CCR3 dependent attraction of Th2 lymphocytes and exert CXCR3‐independent, defensin‐like antibacterial activity.
Identification of a CTL‐directed epitope encoded by an intron of the putative tumor suppressor gene Testin of the common fragile site 7G region: a peptide vaccine candidate for HLA‐B52+ and HLA‐62+ cancer patients
Authors: Ohkouchi Shinya , Kawamoto Naoki , Koga Makoto , Sakanashi Fumi , Shichijo Shigeki , Saijo Yasuo , Nukiwa Toshihiro , Itoh Kyogo , Yamada Akira 
Published: October 2003

AbstractAlthough cytotoxic T lymphocyte (CTL)‐directed epitopes binding to human histocompatibility leukocyte antigen (HLA)‐A molecules have been well characterized, those binding to HLA‐B molecules have not, largely due to their large diversity. In this study we report a unique cancer antigen gene, tentatively named Testin‐related gene (TRG), which encodes CTL‐directed epitopes on the HLA‐B52 molecules most frequently expressed in Asians. TRG is located in an intron of the putative tumor suppressor gene Testin in the common fragile site 7G region at 7q31.2. TRG mRNA was expressed in the majority of cancer cells and cancer tissue tested, whereas it was scarcely expressed in the majority of normal tissues, and only low‐level expression of TRG was detected in the heart, liver, and pancreas. One TRG peptide had the ability to induce HLA‐B52‐restricted CTL cytotoxic to TRG+ tumor cells in peripheral blood mononuclear cells (PBMC) of epithelial cancer patients. This peptidealso induced HLA‐B62‐restricted and tumor‐reactive CTL in PBMC of cancer patients. Therefore, this TRG‐derived peptide might be appropriate for use in peptide‐based immunotherapy for relatively large numbers of cancer patients throughout the world, given that 34% of Japanese, 27% of Chinese, and 13% of Caucasians express either HLA‐B52 or HLA‐B62 molecules
The B subunit of Escherichia coli heat labile enterotoxin abrogates oral tolerance, promoting predominantly Th2‐type immune responses
Authors: Plant Andrea , Williams Rachel , Jackson Michelle E. , Williams Neil A. 
Published: October 2003

AbstractMucosal antigen encounter usually results in a state of systemic non‐responsiveness (tolerance). This failure to mount a protective response is a major hurdle to mucosal vaccine development. Hence, the identification of safe and effective mucosal adjuvants promoting protective immunity is of critical importance. The non‐toxic B subunit of Escherichia coli heat labile enterotoxin(EtxB) is a potent nasal adjuvant; however, its usefulness following oral delivery is unconfirmed. We used DO11.10 chimeric mice to assess whether EtxB could abrogate tolerance to oral OVA. We showthat admixing EtxB with OVA for oral immunization abrogates oral tolerance and results in a weak anti‐OVA immune response. Importantly, EtxB profoundly modulated the nature of the response to subsequent parenteral challenge, promoting IgG1 in favor of IgG2a antibodies and depressing IFN‐γ production while elevating TGF‐β secretion. The addition of EtxB promoted T cell division, as assessed by loss of staining with carboxyfluorescein diacetate succinimidyl ester. Enhanced cell division promoted by EtxB was associated with T cell differentiation (increased numbers of CD45RBlow cells) in vivo, although dividing OVA‐specific T cells were CD25–. These data suggest that although EtxB is a weak oral adjuvant, it can profoundly modulate the nature of the immune response to admixed antigen.
Post‐translational and cell type‐specific regulation of CXCR4 expression by cytokines
Authors: Brühl Hilke , Cohen Clemens D. , Linder Stefan , Kretzler Matthias , Schlöndorff Detlef , Mack Matthias 
Published: October 2003

AbstractWe have investigated the regulation and function of the chemokine receptor CXCR4 on neutrophils. CXCR4 is hardly detectable on neutrophils in the peripheral blood. However, overnight culture strongly up‐regulates CXCR4 expression on the cell surface. The functional activity of CXCR4 on cultured neutrophils was confirmed by stromal cell‐derived factor (SDF)‐induced migration and up‐regulation of the integrins CD11b and CD11c. CXCR4 surface expression on neutrophils but not on lymphocytes and monocytes is rapidly down‐regulated after stimulation with TNF‐α and IFN‐γ, resulting in significantly decreased SDF‐induced functional responses of neutrophils. In contrast to surface expression, CXCR4 mRNA expression was several‐fold increased in cytokine‐stimulated neutrophils, suggesting a post‐translational regulation. By confocal microscopy we demonstrate that CXCR4 is internalized after stimulation with TNF‐α and IFN‐γ. The down‐modulation of CXCR4 surface expression in response to TNF‐α and IFN‐γ was fully reversible after cytokine removal. Further, CXCR4 down‐modulation could be completely blocked by hypertonic sucrose and significantly reduced by chlorpromazine indicating the involvement of clathrin‐coated pits. Internalization of CXCR4 by cytokines in a cell type‐specific manner is a novel and functionally important mechanism of chemokine receptor regulation.