bluuebunny/crossref_metadata_2025_split huggingface dataset:
MR Imaging in Biofix-Osteosynthesis
Authors: Lohman M. , Partio E. K. , Vehmas T. , Kivisaari A. , Kivisaari L. 
Published: October 2009

Purpose: Osteosynthesis by means of bioresorbable implants, mostly of self-reinforced poly-L-lactide (SR-PLLA), has been used in humans for about 10 years. The aim of this study was to examine the controversy between histological studies confirming fragmentation of the biomaterial and radiological studies showing no breaking of the material. Material and Methods: Six patients with displaced malleolar fractures operatively treated with biodegradable SR-PLLA screws underwent MR examinations at 1.5 T, immediately postoperatively and after one to two years. Results: The biodegradable osteosynthetic screws were clearly seen on all MR images. Of 12 screws, 6 were broken at the final examination (5 syndesmotic transfixation screws and 1 screw through the growth cartilage). Conclusion: The breaking of a biodegradable osteosynthesis is possible to document on MR images.
Comparison of bioactive coils and bare platinum coils for treatment of intracranial aneurysms: a matched-pair analysis
Authors: Geyik Serdar , Ertugrul Ozgur , Yavuz Kivilcim , Geyik Pinar , Saatci Isil , Cekirge H. Saruhan 
Published: October 2009

Object
The primary goal of this matched-pair analysis was to evaluate the durability of the treatment results with Cerecyte coils in comparison with that of bare platinum coils in terms of angiographic occlusion rates at follow-up.

Methods
Eighty aneurysms treated with Cerecyte coils were included in this study to carry out a matched-pair analysis. Every aneurysm treated with Cerecyte coils was matched with an aneurysm treated with bare platinum coils. Matching of the aneurysms was done according to the aneurysm size, location, neck size, initial occlusion grade, and clinical presentation.

Results
The initial treatment results were similar in both groups as part of a matching protocol. Subgroup analysis revealed a significant difference in the durability of occlusion in aneurysms that showed Raymond Class I obliteration on follow-up angiograms (69 [86.2%] in the Cerecyte group vs 51 [63.8%] in the control group, p = 0.002). Further thrombosis to Raymond Class I occlusions was higher in the Cerecyte group (17 [77.3%] of 22 vs 8 [36.4%] of 22 aneurysms).

Conclusions
Cerecyte coils provide further thrombosis and more durable results than bare platinum coils following coil embolization of cerebral aneurysms.
A comparison of World Health Organization tumor grades at recurrence in patients with non–skull base and skull base meningiomas
Authors: McGovern Susan L. , Aldape Kenneth D. , Munsell Mark F. , Mahajan Anita , DeMonte Franco , Woo Shiao Y. 
Published: October 2009

Object
Despite a favorable outcome for most patients with WHO Grade I meningiomas, a subset of these patients will have recurrent or progressive disease that advances to a higher grade and requires increasingly aggressive therapy. The goal of this study was to identify clinical characteristics associated with the recurrence of benign meningiomas and their acceleration to atypical and malignant histological types.

Methods
Records of 216 patients with WHO Grade I, II, or III meningioma that were initially treated between 1965 and 2001 were retrospectively reviewed. Median follow-up was 7.2 years.

Results
Patients with non–skull base cranial meningiomas (82 of 105 [78%]) were more likely to have undergone a gross-total resection than patients with skull base meningiomas (32 of 78 [41%]; p < 0.001). Consequently, patients with Grade I non–skull base cranial meningiomas had better 5-year recurrence-free survival (69%) than patients with Grade I skull base meningiomas (56%) or Grade II or III tumors at any site (50%; p = 0.005). Unexpectedly, patients with non–skull base tumors who experienced a recurrence (8 of 22 [36%]) were more likely than patients with skull base tumors (1 of 19 [5%]) to have a higher grade tumor at recurrence (p = 0.024). Furthermore, the median MIB-1 labeling index of Grade I non–skull base cranial meningiomas (2.60%) was significantly higher than that of Grade I skull base tumors (1.35%; p = 0.016).

Conclusions
Cranial meningiomas that occur outside of the skull base are more likely to have a higher MIB-1 labeling index and recur with a higher grade than those within the skull base, suggesting that non–skull base cranial tumors may have a more aggressive biology than skull base tumors.
Increased Expression of IL-33 in Severe Asthma: Evidence of Expression by Airway Smooth Muscle Cells
Authors: Préfontaine David , Lajoie-Kadoch Stéphane , Foley Susan , Audusseau Séverine , Olivenstein Ron , Halayko Andrew J. , Lemière Catherine , Martin James G. , Hamid Qutayba 
Published: October 2009

Abstract
IL-33, a new member of the IL-1 cytokine family, promotes Th2 inflammation, but evidence on the implications of this cytokine in asthma is lacking. IL-33 would be mainly expressed by structural cells, but whether proinflammatory cytokines modulate its expression in airway smooth muscle cells (ASMC) is unknown. Endobronchial biopsies were obtained from adults with mild (n = 8), moderate (n = 8), severe (n = 9), asthma and from control subjects (n = 5). Immunocytochemistry, laser-capture microdissection, reverse transcriptase, and real-time quantitative PCR were used for determining IL-33 expression in the lung tissues. ASMC isolated from resected lung specimens were cultured with proinflammatory cytokines and with dexamethasone. IL-33 expression by ASMC was determined by PCR, ELISA, and Western blotting. Higher levels of IL-33 transcripts are detected in biopsies from asthmatic compared with control subjects, and especially in subjects with severe asthma. ASMC show IL-33 expression at both protein and mRNA levels. IL-33 and TNF-α transcript levels correlate in the lung tissues, and TNF-α up-regulates IL-33 expression by cultured ASMC in a time- and dose-dependent manner. IFN-γ also increases IL-33 expression and shows synergistic effect with TNF-α. Dexamethasone fails to abolish TNF-α-induced IL-33 up-regulation. IL-33 expression increases in bronchial biopsies from subjects with asthma compared with controls, as well as subjects with asthma severity. ASMC are a source of the IL-33 cytokine. Our data propose IL-33 as a novel inflammatory marker of severe and refractory asthma.
In Vivo Expansion of Activated Naive CD8+ T Cells and NK Cells Driven by Complexes of IL-2 and Anti-IL-2 Monoclonal Antibody As Novel Approach of Cancer Immunotherapy
Authors: Tomala Jakub , Chmelova Helena , Mrkvan Tomas , Rihova Blanka , Kovar Marek 
Published: October 2009

Abstract
IL-2 is potent imunostimulatory molecule that plays a key role in T and NK cell activation and expansion. IL-2 is approved by the FDA to treat metastatic renal cancer and melanoma, but its extremely short half-life and serious toxicities are significant limitations of its use. It was reported that in vivo biological activity of IL-2 can be increased by association of IL-2 with anti-IL-2 mAb (S4B6). IL-2/S4B6 mAb immunocomplexes were described to be highly stimulatory for NK and memory CD8+ T cells and intermediately also for regulatory T cells. IL-2/JES6-1 mAb immunocomplexes are stimulatory solely for regulatory T cells. In this study we show that although both mentioned IL-2 immunocomplexes are less potent than free IL-2 in vitro, they possess extremely high stimulatory activity to expand activated naive CD8+ T cells in vivo. IL-2 immunocomplexes expand activated naive CD8+ T cells several hundred-fold times after four doses and more than 1000-fold times after six doses (1.5 μg/dose of IL-2), whereas free IL-2 given at the same dosage shows negligible activity. IL-2/S4B6 mAb immunocomplexes also induce massive expansion of NK cells (40% of DX5+NK1.1+ cells in spleen). Importantly, activated naive CD8+ T cells expanded by IL-2 immunocomplexes form robust population of functional memory cells. We also demonstrate in two distinct tumor models that IL-2/S4B6 mAb immunocomplexes possess considerable antitumor activity. Finally, by using radioactively labeled IL-2, we provide for first time direct evidence that IL-2 immunocomplexes have much longer half-life in circulation than free IL-2, being ∼3 h vs &lt;15 min, respectively.
Cutting Edge: Responder T Cells Regulate Human DR+ Effector Regulatory T Cell Activity via Granzyme B
Authors: Ashley Charles W. , Baecher-Allan Clare 
Published: October 2009

Abstract
MHC class II expression identifies an effector subset of human CD4+CD25highFoxP3high natural regulatory T cells (DR+ Tregs) that induces more rapid suppression and exhibits higher FoxP3 expression than the remaining Treg population. Although Tregs are known to be highly sensitive to apoptosis, in this study we demonstrate that this sensitivity is primarily a feature of DR+ Tregs. Granzyme B (GzmB) is strongly expressed by nonregulatory responder CD4 T cells, whereas effector DR+ Tregs express little GzmB. Strong TCR stimulation markedly increases the expression of GzmB in all dividing responder CD4 T cells and mitigates the suppression by DR+ Tregs. DR+ Treg suppressive activity reemerges if GzmB is neutralized. We show that responder cells actively kill effector Tregs by producing GzmB in response to strong TCR stimulation. Thus, the production of GzmB by strongly activated CD4 T cells represents a mechanism by which CD4 T cells resist Treg suppression.
CD94 Defines Phenotypically and Functionally Distinct Mouse NK Cell Subsets
Authors: Yu Jianhua , Wei Min , Mao Hsiaoyin , Zhang Jianying , Hughes Tiffany , Mitsui Takeki , Park Il-kyoo , Hwang Christine , Liu Shujun , Marcucci Guido , Trotta Rossana , Benson Don M. , Caligiuri Michael A. 
Published: October 2009

Abstract
Understanding of heterogeneous NK subsets is important for the study of NK cell biology and development, and for the application of NK cell-based therapies in the treatment of disease. Here we demonstrate that the surface expression of CD94 can distinctively divide mouse NK cells into two approximately even CD94low and CD94high subsets in all tested organs and tissues. The CD94high NK subset has significantly greater capacity to proliferate, produce IFN-γ, and lyse target cells than does the CD94low subset. The CD94high subset has exclusive expression of NKG2A/C/E, higher expression of CD117 and CD69, and lower expression of Ly49D (activating) and Ly49G2 (inhibitory). In vivo, purified mouse CD94low NK cells become CD94high NK cells, but not vice versa. Collectively, our data suggest that CD94 is an Ag that can be used to identify functionally distinct NK cell subsets in mice and could also be relevant to late-stage mouse NK cell development.
Cutting Edge: Importance of IL-6 and Cooperation between Innate and Adaptive Immune Receptors in Cellular Vaccination with B Lymphocytes
Authors: Vanden Bush Tony J. , Buchta Claire M. , Claudio Jennifer , Bishop Gail A. 
Published: October 2009

Abstract
B lymphocytes are a potential alternative to dendritic cell immunotherapy, with the advantages of relative abundance in peripheral blood and the ability to function as APCs. Although B cells express multiple receptors that induce costimulatory molecules, B cell vaccine studies have focused primarily on CD40 stimulation. To optimize the potential efficacy of B cell vaccines (Bvac), we compared the capacity of differentially stimulated B cells to induce Ag-specific CD8+ T cell responses in vivo. CD40- or TLR7-stimulated B cell APCs induced similar CD8+ T cell responses, but costimulation through the BCR and TLR7 produced a more effective Bvac as measured by T cell stimulation and the protection of mice from an infectious pathogen. This increased effectiveness depended upon enhanced production of IL-6 by BCR plus TLR7-stimulated B cells. These findings reveal alternative stimulation strategies for the production of effective Bvac and identify a key role for IL-6 in B cell Ag presentation and cellular vaccines.
Primary Human Tumor Cells Expressing CD155 Impair Tumor Targeting by Down-Regulating DNAM-1 on NK Cells
Authors: Carlsten Mattias , Norell Håkan , Bryceson Yenan T. , Poschke Isabel , Schedvins Kjell , Ljunggren Hans-Gustaf , Kiessling Rolf , Malmberg Karl-Johan 
Published: October 2009

Abstract
The activating NK cell receptor DNAX accessory molecule-1 (DNAM-1) contributes to tumor immune surveillance and plays a crucial role in NK cell-mediated recognition of several types of human tumors, including ovarian carcinoma. Here, we have analyzed the receptor repertoire and functional integrity of NK cells in peritoneal effusions from patients with ovarian carcinoma. Relative to autologous peripheral blood NK cells, tumor-associated NK cells expressed reduced levels of the DNAM-1, 2B4, and CD16 receptors and were hyporesponsive to HLA class I-deficient K562 cells and to coactivation via DNAM-1 and 2B4. Moreover, tumor-associated NK cells were also refractory to CD16 receptor stimulation, resulting in diminished Ab-dependent cellular cytotoxicity against autologous tumor cells. Coincubation of NK cells with ovarian carcinoma cells expressing the DNAM-1 ligand CD155 led to reduction of DNAM-1 expression. Therefore, NK cell-mediated rejection of ovarian carcinoma may be limited by perturbed DNAM-1 expression on tumor-associated NK cells induced by chronic ligand exposure. Thus, these data support the notion that tumor-induced alterations of activating NK cell receptor expression may hamper immune surveillance and promote tumor progression.
The E3 Ubiquitin Ligase Cbl-b Regulates Expansion but Not Functional Activity of Self-Reactive CD4 T Cells
Authors: St. Rose Marie-Clare , Qui Harry Z. , Bandyopadhyay Suman , Mihalyo Marianne A. , Hagymasi Adam T. , Clark Robert B. , Adler Adam J. 
Published: October 2009

Abstract
Cbl-b is an E3 ubiquitin ligase that limits Ag responsiveness in T cells by targeting TCR-inducible signaling molecules. Cbl-b deficiency thus renders T cells hyperresponsive to antigenic stimulation and predisposes individuals toward developing autoimmunity. In part because Cbl-b−/− T cells do not require CD28 costimulation to become activated, and insufficient costimulation is a critical parameter that confers anergy induction over effector differentiation, it has been hypothesized that Cbl-b−/− T cells are resistant to anergy. This possibility has been supported in models in which anergy is normally induced in vitro, or in vivo following exposure to soluble Ag boluses. In the current study, we characterized the response of Cbl-b−/− CD4 T cells in an in vivo system in which anergy is normally induced by a constitutively expressed peripheral self-Ag. Cbl-b expression increased in self-Ag-induced anergic wild-type CD4 T cells, and Cbl-b−/− CD4 T cells underwent more robust proliferation and expansion upon initially encountering cognate self-Ag compared with wild-type counterparts. Nevertheless, both wild-type and Cbl-b−/− CD4 T cells ultimately developed the same impaired ability to respond to antigenic restimulation. The more extensive expansion that occurred during the initial induction of anergy did, however, allow the anergic CD4 T cells to expand to greater numbers when they were functionally resuscitated following replacement of the initial source of tolerizing self-Ag with a viral form of the same Ag.
Dominant Role of Antigen Dose in CD4+Foxp3+ Regulatory T Cell Induction and Expansion
Authors: Turner Michael S. , Kane Lawrence P. , Morel Penelope A. 
Published: October 2009

Abstract
The definitions of tolerogenic vs immunogenic dendritic cells (DC) remain controversial. Immature DC have been shown to induce T regulatory cells (Treg) specific for foreign and allogeneic Ags. However, we have previously reported that mature DC (mDC) prevented the onset of autoimmune diabetes, whereas immature DC (iDC) were therapeutically ineffective. In this study, islet-specific CD4+ T cells from BDC2.5 TCR-transgenic mice were stimulated in the absence of exogenous cytokine with iDC or mDC pulsed with high- or low-affinity antigenic peptides and examined for Treg induction. Both iDC and mDC presenting low peptide doses induced weak TCR signaling via the Akt/mammalian target of rapamycin (mTOR) pathway, resulting in significant expansion of Foxp3+ Treg. Furthermore, unpulsed mDC, but not iDC, also induced Treg. High peptide doses induced strong Akt/mTOR signaling and favored the expansion of Foxp3neg Th cells. The inverse correlation of Foxp3 and Akt/mTOR signaling was also observed in DO11.10 and OT-II TCR-transgenic T cells and was recapitulated with anti-CD3/CD28 stimulation in the absence of DC. IL-6 production in these cultures correlated positively with Ag dose and inversely with Treg expansion. Studies with T cells or DC from IL-6−/− mice revealed that IL-6 production by T cells was more important in the inhibition of Treg induction at low Ag doses. These studies indicate that the strength of Akt/mTOR signaling, a critical T cell-intrinsic determinant for Treg vs Th induction, can be controlled by adjusting the dose of antigenic peptide. Furthermore, this operates in a dominant fashion over DC phenotype and cytokine production.
TCR Down-Regulation Controls T Cell Homeostasis
Authors: Boding Lasse , Bonefeld Charlotte Menné , Nielsen Bodil L. , Lauritsen Jens Peter H. , von Essen Marina Rode , Hansen Ann Kathrine , Larsen Jeppe Madura , Nielsen Morten Milek , Ødum Niels , Geisler Carsten 
Published: October 2009

Abstract
TCR and cytokine receptor signaling play key roles in the complex homeostatic mechanisms that maintain a relative stable number of T cells throughout life. Despite the homeostatic mechanisms, a slow decline in naive T cells is typically observed with age. The CD3γ di-leucine-based motif controls TCR down-regulation and plays a central role in fine-tuning TCR expression and signaling in T cells. In this study, we show that the age-associated decline of naive T cells is strongly accelerated in CD3γLLAA knock-in mice homozygous for a double leucine to alanine mutation in the CD3γ di-leucine-based motif, whereas the number of memory T cells is unaffected by the mutation. This results in premature T cell population senescence with a severe dominance of memory T cells and very few naive T cells in middle-aged to old CD3γ mutant mice. The reduced number of naive T cells in CD3γ mutant mice was caused by the combination of reduced thymic output, decreased T cell apoptosis, and increased transition of naive T cells to memory T cells. Experiments with bone marrow chimeric mice confirmed that the CD3γLLAA mutation exerted a T cell intrinsic effect on T cell homeostasis that resulted in an increased transition of CD3γLLAA naive T cells to memory T cells and a survival advantage of CD3γLLAA T cells compared with wild-type T cells. The experimental observations were further supported by mathematical modeling of T cell homeostasis. Our study thus identifies an important role of CD3γ-mediated TCR down-regulation in T cell homeostasis.
Acquisition of T Regulatory Function in Cathepsin L-Inhibited T Cells by Eye-Derived CTLA-2α during Inflammatory Conditions
Authors: Sugita Sunao , Horie Shintaro , Nakamura Orie , Maruyama Kazuichi , Takase Hiroshi , Usui Yoshihiko , Takeuchi Masaru , Ishidoh Kazumi , Koike Masato , Uchiyama Yasuo , Peters Christoph , Yamamoto Yoshimi , Mochizuki Manabu 
Published: October 2009

Abstract
Pigment epithelium isolated from the eye possesses immunosuppressive properties such as regulatory T (Treg) cell induction; e.g., cultured retinal pigment epithelium (RPE) converts CD4+ T cells into Treg cells in vitro. RPE constitutively expresses a novel immunosuppressive factor, CTLA-2α, which is a cathepsin L (CathL) inhibitor, and this molecule acts via RPE to induce Treg cells. To clarify CTLA-2α’s role in the T cell response to RPE in ocular inflammation, we used the experimental autoimmune uveitis (EAU) animal model to examine this new immunosuppressive property of RPE. In EAU models, TGF-β, but not IFN-γ inflammatory cytokines, promotes the up-regulation of the expression of CTLA-2α in RPE. Similarly, CTLA-2α via RPE was able to promote TGF-β production by the CD4+ T cells. The RPE-exposed T cells (RPE-induced Treg cells) greatly produced TGF-β and suppressed bystander effector T cells. There was less expression of CathL by the RPE-exposed T cells, and CathL-inhibited T cells were able to acquire the Treg phenotype. Moreover, CathL-deficient mice spontaneously produced Treg cells, with the increase in T cells potentially providing protection against ocular inflammation. More importantly, CD4+ T cells from EAU in CathL knockout mice or rCTLA-2α from EAU animals were found to contain a high population of forkhead box p3+ T cells. In both EAU models, there was significant suppression of the ocular inflammation. These results indicate that RPE secretes CTLA-2α, thereby enabling the bystander T cells to be converted into Treg cells via TGF-β promotion.
Recombination Signal Sequence-Associated Restriction on TCRδ Gene Rearrangement Affects the Development of Tissue-Specific γδ T Cells
Authors: Uche Uzodinma N. , Huber Christopher R. , Raulet David H. , Xiong Na 
Published: October 2009

Abstract
Assembly of TCRα and TCRδ genes from the TCRα/δ locus is tightly controlled for the proper generation of αβ and γδ T cells. Of &gt;100 shared variable gene segments in the TCRα/δ locus, only a few are predominantly used for the TCRδ gene assembly, while most are for TCRα. However, the importance and mechanisms of the selective variable gene rearrangement for T cell development are not fully understood. We report herein that the development of a tissue-specific γδ T cell population is critically affected by recombination signal sequence-associated restriction on the variable gene usage for TCRδ assembly. We found that the development of substitute skin γδ T cells in mice deficient of the TCRγ3 gene, which is used in wild-type skin γδ T cells, was drastically affected by the strain background. A Vγ2+ skin γδ T cell population developed in mice of the B6 but not the 129 strain backgrounds, due to a difference in the rearrangement of endogenous Vδ7+ TCRδ genes, which paired with the Vγ2+ TCRγ gene to generate the Vγ2/Vδ7+ skin γδ T cell precursors in fetal thymi of the B6 background mice. The defective TCRδ rearrangement of the 129-“Vδ7” gene was associated with specific variations in its recombination signal sequence, which renders it poorly compatible for rearrangement to Dδ genes. These findings provide the first direct evidence that recombination signal sequence-associated restriction on the variable gene usage for TCRα/δ gene assembly plays an important role in T cell development.
Langerhans Cells Suppress Contact Hypersensitivity Responses Via Cognate CD4 Interaction and Langerhans Cell-Derived IL-10
Authors: Igyarto Botond Z. , Jenison Matthew C. , Dudda Jan C. , Roers Axel , Müller Werner , Koni Pandelakis A. , Campbell Daniel J. , Shlomchik Mark J. , Kaplan Daniel H. 
Published: October 2009

Abstract
Mice lacking epidermal Langerhans cells (LC) develop exaggerated contact-hypersensitivity (CHS) responses due to the absence of LC during sensitization/initiation. Examination of T cell responses reveals that the absence of LC leads to increased numbers of hapten-specific CD4 and CD8 T cells but does not alter cytokine expression or development of T regulatory cells. CHS responses and Ag-specific T cells are increased in mice in which MHC class II is ablated specifically in LC suggesting that direct cognate interaction between LC and CD4 cells is required for suppression. LC-derived IL-10 is also required for optimal inhibition of CHS. Both LC-derived IL-10-mediated suppression and full LC activation require LC expression of MHC class II. These data support a model in which cognate interaction of LC with CD4 T cells enables LC to inhibit expansion of Ag-specific responses via elaboration of IL-10.