bluuebunny/crossref_metadata_2025_split huggingface dataset:
Early functional outcomes and histological analysis after spinal cord compression injury in rats
Authors: Lonjon Nicolas , Kouyoumdjian Pascal , Prieto Monica , Bauchet Luc , Haton Henri , Gaviria Manuel , Privat Alain , Perrin Florence E. 
Published: December 2009

Object
Neuroprotective and repair strategies in spinal cord injuries (SCIs) have been so far largely unsuccessful. One of the prerequisites is the use of appropriate preclinical models to decipher pathophysiological mechanisms; another is the identification of optimal time windows for therapeutic interventions. The authors undertook this study to characterize early motor, sensory, autonomic, and histological outcomes after balloon compression of the spinal cord at the T8–9 level in adult rats.

Methods
A total of 91 rats were used in this study. Spinal cord balloon compression was performed at T8–9 in adult rats by inflation of a 2 Fr Fogarty catheter into the epidural space. The authors first characterized early motor, sensory, and autonomic outcomes of 2 volumes of compression (10 and 15 μl) using behavioral tests and then examined histological outcomes in the spinal cord using Luxol fast blue staining. To further substantiate the characterization of the epidural balloon-compression model, they used a noncompetitive N-methyl-d-aspartate antagonist, GK11, and demonstrated the involvement of excitotoxicity in this model.

Results
Proportional and reproducible functional impairment resulted from compression caused by balloon inflation with either 10 or 15 μl of water and corresponded to the extent of the lesion. Indeed, during the early phase following SCI (1 week postinjury), recovery of locomotor function and bladder control correlated with the volume of inflation, whereas outcomes with respect to sensory function and reflexes were independent of compression severity. Treatment with GK11 significantly improved motor function in all groups of rats 1 week after injury and bladder voiding in the 10-μl injured rats compared to the 15-μl injured rats.

Conclusions
The results of this study demonstrate that spinal balloon-compression injury in the rat is a well-characterized, reproducible, and predictable model to analyze early events following SCI.
Seizure control outcomes after resection of dysembryoplastic neuroepithelial tumor in 50 patients
Authors: Chang Edward F. , Christie Catherine , Sullivan Joseph E. , Garcia Paul A. , Tihan Tarik , Gupta Nalin , Berger Mitchel S. , Barbaro Nicholas M. 
Published: December 2009

Object
Dysembryoplastic neuroepithelial tumors (DNETs) are a subset of relatively rare glioneuronal tumors that typically present with epilepsy during childhood. The authors' aim was to identify factors that predict seizure control following excision.

Methods
The authors reviewed the cases of 50 patients who underwent resection of DNETs at the University of California, San Francisco, between 1990 and 2006. Demographic, seizure history, radiographic, and histopathological data were collected and analyzed for statistical association with postoperative seizure control.

Results
Of the 50 patients, 86% presented with intractable epilepsy. The median age at surgery was 21 years (range 4–46 years; 40% were < 18 years old at time of surgery), with a median duration of 8 years from onset of seizures (24% were adult-onset seizures). Fifty-two percent of the cases were associated with adjacent focal cortical dysplasia. Complete resection was achieved in 78% of cases. Intraoperative electrocorticography in 23 patients identified extralesional interictal activity in 16 cases, which led to extended lesionectomy or lobectomy. The remaining patients underwent lesionectomy alone. The median follow-up was 5.6 years, during which time tumor progression occurred after subtotal resection. The proportional estimates of seizure freedom (Engel Class I outcome) were 0.86 at 1 year and 0.85 at 5 years. Seizure freedom was predicted by complete or extended resection (OR 1.68, 95% CI 1.39–2.03; p < 0.0001) and extratemporal location (OR 1.20, 95% CI 1.02–1.42; p = 0.03) on multivariate analysis. Secondary analysis for intraoperative electrocorticography cases demonstrated that seizure outcome was better when extralesional spiking foci were detected (94% seizure free) compared with when they were absent (43% seizure free).

Conclusions
Excision of DNETs and, when present, adjacent dysplastic cortex was highly effective for seizure control. Excellent seizure-free outcomes and tumor control were seen with lesionectomy alone in most cases. Electrocorticography with extended resection was useful for patients with pharmacoresistant epilepsy.
Use of the Gartland Classification System for Treatment of Pediatric Supracondylar Humerus Fractures
Authors: Mallo Gregory , Stanat Scott J.C. , Gaffney John 
Published: January 2010

The extension-type pediatric supracondylar humerus fracture accounts for nearly two-thirds of all pediatric hospitalizations due to elbow trauma. The Gartland classification guides the standard of care for treatment of this entity. Type I injuries are treated with cast immobilization while type II and III injuries are treated operatively. The reported interobserver reliability ranges from moderate to full agreement, which is on par with other frequently referenced classification systems such as Lauge-Hansen for adult ankle fractures.
In this study, 4 fellowship-trained pediatric orthopedic surgeons reviewed radiographs of 72 pediatric supracondylar fractures and classified them based on Gartland's system. They recommended their preferred treatment of cast immobilization for type I fractures and of closed reduction and pinning in the operating room for type II and type III fractures. The interobserver and intraobserver reliability for each set of radiographs was then analyzed.
There was moderate agreement comparing all fractures and comparing types I and II fractures, while there was full agreement for type III fractures. There was full agreement for the intraobserver reliability. The preferred treatment (casting vs operative intervention) differed in 35% of patients, if based on the fracture classification.
Matrix Metalloproteinase-8 Inactivates Macrophage Inflammatory Protein-1α To Reduce Acute Lung Inflammation and Injury in Mice
Authors: Quintero Pablo A. , Knolle Martin D. , Cala Luisa F. , Zhuang Yuehong , Owen Caroline A. 
Published: December 2009

Abstract
To determine the role of matrix metalloproteinase-8 (MMP-8) in acute lung injury (ALI), we delivered LPS or bleomycin by the intratracheal route to MMP-8−/− mice versus wild-type (WT) mice or subjected the mice to hyperoxia (95% O2) and measured lung inflammation and injury at intervals. MMP-8−/− mice with ALI had greater increases in lung polymorphonuclear neutrophils (PMNs) and macrophage counts, measures of alveolar capillary barrier injury, lung elastance, and mortality than WT mice with ALI. Bronchoalveolar lavage fluid (BALF) from LPS-treated MMP-8−/− mice had more MIP-1α than BALF from LPS-treated WT mice, but similar levels of other pro- and anti-inflammatory mediators. MIP-1α−/− mice with ALI had less acute lung inflammation and injury than WT mice with ALI, confirming that MIP-1α promotes acute lung inflammation and injury in mice. Genetically deleting MIP-1α in MMP-8−/− mice reduced the increased lung inflammation and injury and mortality in MMP-8−/− mice with ALI. Soluble MMP-8 cleaved and inactivated MIP-1α in vitro, but membrane-bound MMP-8 on activated PMNs had greater MIP-1α–degrading activity than soluble MMP-8. High levels of membrane-bound MMP-8 were detected on lung PMNs from LPS-treated WT mice, but soluble, active MMP-8 was not detected in BALF samples. Thus, MMP-8 has novel roles in restraining lung inflammation and in limiting alveolar capillary barrier injury during ALI in mice by inactivating MIP-1α. In addition, membrane-bound MMP-8 on activated lung PMNs is likely to be the key bioactive form of the enzyme that limits lung inflammation and alveolar capillary barrier injury during ALI.
TLR2-Dependent Inflammatory Response to Porphyromonas gingivalis Is MyD88 Independent, whereas MyD88 Is Required To Clear Infection
Authors: Burns Elia , Eliyahu Tal , Uematsu Satoshi , Akira Shizuo , Nussbaum Gabriel 
Published: December 2009

Abstract
Porphyromonas gingivalis is a Gram-negative anaerobe considered to be a major periodontal pathogen. TLR2 plays a central role in the response to P. gingivalis infection in vivo. In its absence there is a weak inflammatory response; however, bacteria are cleared rapidly compared with wild-type mice. We examined the role of the TLR adaptor proteins MyD88 and TLR/IL-1R–domain-containing adaptor-inducing IFN-β in the inflammatory response to P. gingivalis in vivo and in the ability to clear the bacterial infection. Proinflammatory cytokine production in response to P. gingivalis infection depends on TLR2, but it does not require MyD88 or TLR/IL-1R–domain-containing adaptor-inducing IFN-β. In contrast, the generation of intracellular toxic oxygen species and the ultimate clearance of P. gingivalis infection depend critically on MyD88, independent of TLR2. Thus, robust cytokine production and bacterial clearance are independent events mediated by distinct signaling pathways following infection with P. gingivalis.
Critical Role of IL-1 Receptor-Associated Kinase-M in Regulating Chemokine-Dependent Deleterious Inflammation in Murine Influenza Pneumonia
Authors: Seki Masafumi , Kohno Shigeru , Newstead Michael W. , Zeng Xianying , Bhan Urvashi , Lukacs Nicholas W. , Kunkel Steven L. , Standiford Theodore J. 
Published: December 2009

AbstractInfluenza virus is a common cause of respiratory infection and morbidity, which is often due to deleterious host immune responses directed against the pathogen. We investigated the role of IL-1 receptor-associated kinase-M (IRAK-M), an inhibitor of MyD88-dependent TLR signaling, in modulating the innate inflammatory response during influenza pneumonia using a murine model. The intranasal administration of influenza resulted in the upregulation of IRAK-M mRNA and protein levels in the lungs within 2 d after infectious challenge. Pulmonary influenza infection in mice deficient in IRAK-M (IRAK-M−/−) resulted in substantially increased mortality compared with similarly treated wild-type animals. Increased mortality in IRAK-M−/− mice was associated with enhanced early influx of neutrophils, high permeability edema, apoptosis of lung epithelial cells, markedly increased expression of inflammatory cytokines/chemokines, and release of neutrophil-derived enzymes, including myeloperoxidase and neutrophil elastase. Early viral clearance was not different in mutant mice, whereas viral titers in lungs and blood were significantly higher in IRAK-M−/−mice compared with wild-type animals. Increased lethality observed in IRAK-M−/− mice after influenza challenge was abrogated by Ab-mediated blockade of CXCR2. Collectively, our findings indicate that IRAK-M is critical to preventing deleterious neutrophil-dependent lung injury during influenza infection of the respiratory tract.
LL-37 Promotes Rapid Sensing of CpG Oligodeoxynucleotides by B Lymphocytes and Plasmacytoid Dendritic Cells
Authors: Hurtado Plinio , Au Peh Chen 
Published: December 2009

AbstractLL-37 is a cationic antimicrobial peptide derived from neutrophils and keratinocytes. It plays an important role in protection against bacterial infection in the skin and mucosal surfaces. However, its role within the blood compartment remains unclear given that serum inhibits its bactericidal property. In this study, we show that LL-37 promotes very rapid and highly efficient sensing of CpG motifs in bacterial DNA by human B lymphocytes and plasmacytoid dendritic cells (pDCs) in serum-containing media and in whole blood. LL-37 allowed detection of CpG oligodeoxynucleotide (ODN) within minutes of exposure. Without LL-37, 20–30 times more CpG was required to produce the same effect. The promotion of CpG detection by LL-37 was independent of the backbone of the ODN, as the effect was observed not only in ODNs with modified phosphorothioate backbone, but also in ODNs with natural phosphodiester backbone, as found in genomic DNA. Unmethylated CpG motifs within the phosphodiester ODN and LL-37–mediated delivery are required for pDCs to respond. In keeping with the above, cells responded to CpG-rich bacterial DNA and LL-37, but not to human DNA and LL-37. The ability of LL-37 to enhance delivery of CpG to stimulate immune cells is independent of its amphipathic structure and its bactericidal property. LL-37 aids the delivery of CpG to B cells and pDCs, but not T cells. These findings are pertinent to rapid recognition of microbial DNA and are highly relevant to contemporary studies of CpG/TLR9 agonists in vaccines and cancer therapy.
IL-17 Regulates CXCL1 mRNA Stability via an AUUUA/Tristetraprolin-Independent Sequence
Authors: Datta Shyamasree , Novotny Michael , Pavicic Paul G. , Zhao Chenyang , Herjan Tomasz , Hartupee Justin , Hamilton Thomas 
Published: December 2009

Abstract
IL-17 contributes to inflammatory response in part by promoting enhanced expression of chemokines, such as CXCL1, by prolonging the t1/2 of this constitutively unstable mRNA. Although IL-17 is a weak stimulus for transcription of the CXCL1 gene, it strongly potentiates message accumulation via stabilization when the mRNA is transcribed in cells stimulated with TNF. In myeloid cells, LPS-induced CXCL1 mRNA stabilization is dependent on AUUUA-containing sequence motifs that are recognized by the RNA binding protein tristetraprolin (TTP). Using deletion and site-specific mutagenesis, we report that IL-17–mediated stabilization of CXCL1 mRNA in nonmyeloid cells depends on a sequence that does not contain the AUUUA motif. Furthermore, a specific two-nucleotide mutation within this region markedly abrogates sensitivity for IL-17–mediated stabilization. Consistent with this finding, the IL-17–sensitive sequence does not exhibit increased instability in the presence of TTP, and CXCL1 mRNA remains unstable and can be stabilized in response to treatment with IL-17 in embryo fibroblasts from mice in which the TTP gene has been deleted. Whereas the RNA binding protein KSRP has been shown to participate in regulating the instability of human CXCL8 mRNA, inhibitory RNA-based reduction in KSRP does not effect the instability mediated by the IL-17–sensitive sequence motif. These findings suggest that IL-17–mediated chemokine mRNA stabilization in nonmyeloid cells uses a mechanism that is distinct from that operating to control AU-rich mRNA stability in myeloid cells.
Regulation of Lentivirus Neurovirulence by Lipopolysaccharide Conditioning: Suppression of CXCL10 in the Brain by IL-10
Authors: Maingat Ferdinand , Viappiani Serena , Zhu Yu , Vivithanaporn Pornpun , Ellestad Kristofor K. , Holden Janet , Silva Claudia , Power Christopher 
Published: December 2009

Abstract
Lentivirus infections including HIV and feline immunodeficiency virus (FIV) cause neurovirulence, which is largely mediated by innate immunity. To investigate the interactions between neurovirulence and repeated conditioning by innate immune activation, models of lentivirus infection were exposed to LPS. Gene expression in HIV-infected (HIV+) and control (HIV−) patient brains was compared by real time RT-PCR and immunocytochemistry. Supernatants from mock and HIV-infected monocyte-derived macrophages exposed to LPS were applied to human neurons. FIV-infected (FIV+) and control (FIV−) animals were exposed repeatedly to LPS postinfection together with concurrent neurobehavioral testing, viral load, and host gene analyses. Brains from HIV+ individuals exhibited induction of CD3ε, CXCL10, and granzyme A expression (p &lt; 0.05). Supernatants from HIV+ monocyte-derived macrophages induced CXCL10 expression in neurons, which was diminished by IL-10 treatment (p &lt; 0.05). LPS-exposed FIV+ animals demonstrated lower plasma and brain viral loads (p &lt; 0.05). Neuronal CXCL10 expression was increased in FIV+ animals but was suppressed by LPS exposure, together with reduced brain CD3ε and granzyme A expression (p &lt; 0.05). In conjunction with preserved NeuN-positive neuronal counts in parietal cortex (p &lt; 0.05), FIV+ animals exposed to LPS also showed less severe neurobehavioral deficits (p &lt; 0.05). Repeated LPS exposures suppressed CXCL10 in the brain and ensuing T cell infiltration with a concomitant reduction in neurovirulence. Thus, innate immune chronic conditioning exerted beneficial effects on neurovirulence through suppression of a specific chemotactic factor, CXCL10, mediated by IL-10, leading to reduced leukocyte infiltration and release of neurotoxic factors.
Cell Type-Specific Recognition of Human Metapneumoviruses (HMPVs) by Retinoic Acid-Inducible Gene I (RIG-I) and TLR7 and Viral Interference of RIG-I Ligand Recognition by HMPV-B1 Phosphoprotein
Authors: Goutagny Nadege , Jiang Zhaozhao , Tian Jane , Parroche Peggy , Schickli Jeanne , Monks Brian G. , Ulbrandt Nancy , Ji Hong , Kiener Peter A. , Coyle Anthony J. , Fitzgerald Katherine A. 
Published: December 2009

Abstract
Human metapneumoviruses (HMPVs) are recently identified Paramyxoviridae that contribute to respiratory tract infections in children. No effective treatments or vaccines are available. Successful defense against virus infection relies on early detection by germ line-encoded pattern recognition receptors and activation of cytokine and type I IFN genes. Recently, the RNA helicase retinoic acid-inducible gene I (RIG-I) has been shown to sense HMPV. In this study, we investigated the abilities of two prototype strains of HMPV (A1 [NL\1\00] and B1 [NL\1\99]) to activate RIG-I and induce type I IFNs. Despite the abilities of both HMPV-A1 and HMPV-B1 to infect and replicate in cell lines and primary cells, only the HMPV-A1 strain triggered RIG-I to induce IFNA/B gene transcription. The failure of the HMPV-B1 strain to elicit type I IFN production was dependent on the B1 phosphoprotein, which specifically prevented RIG-I–mediated sensing of HMPV viral 5′ triphosphate RNA. In contrast to most cell types, plasmacytoid dendritic cells displayed a unique ability to sense both HMPV-A1 and HMPV-B1 and in this case sensing was via TLR7 rather than RIG-I. Collectively, these data reveal differential mechanisms of sensing for two closely related viruses, which operate in cell type‑specific manners.
Mycolactone Suppresses T Cell Responsiveness by Altering Both Early Signaling and Posttranslational Events
Authors: Boulkroun Sheerazed , Guenin-Macé Laure , Thoulouze Maria-Isabel , Monot Marc , Merckx Anaïs , Langsley Gordon , Bismuth Georges , Di Bartolo Vincenzo , Demangel Caroline 
Published: December 2009

AbstractMycolactone is a diffusible lipid toxin produced by Mycobacterium ulcerans, the causative agent of a necrotizing skin disease referred to as Buruli ulcer. Intriguingly, patients with progressive lesions display a systemic suppression of Th1 responses that resolves on surgical excision of infected tissues. In this study, we examined the effects of mycolactone on the functional biology of T cells and identified two mechanisms by which mycolactone suppresses cell responsiveness to antigenic stimulation. At noncytotoxic concentrations, mycolactone blocked the activation-induced production of cytokines by a posttranscriptional, mammalian target of rapamycin, and cellular stress-independent mechanism. In addition, mycolactone triggered the lipid-raft association and activation of the Src-family kinase, Lck. Mycolactone-mediated hyperactivation of Lck resulted in the depletion of intracellular calcium stores and downregulation of the TCR, leading to impaired T cell responsiveness to stimulation. These biochemical alterations were not observed when T cells were exposed to other bacterial lipids, or to structurally related immunosuppressors. Mycolactone thus constitutes a novel type of T cell immunosuppressive agent, the potent activity of which may explain the defective cellular responses in Buruli ulcer patients.
Peripheral Blood CCR4+CCR6+ and CXCR3+CCR6+ CD4+ T Cells Are Highly Permissive to HIV-1 Infection
Authors: Gosselin Annie , Monteiro Patricia , Chomont Nicolas , Diaz-Griffero Felipe , Said Elias A. , Fonseca Simone , Wacleche Vanessa , El-Far Mohamed , Boulassel Mohamed-Rachid , Routy Jean-Pierre , Sekaly Rafick-Pierre , Ancuta Petronela 
Published: December 2009

Abstract
There is limited knowledge on the identity of primary CD4+ T cell subsets selectively targeted by HIV-1 in vivo. In this study, we established a link between HIV permissiveness, phenotype/homing potential, and lineage commitment in primary CD4+ T cells. CCR4+CCR6+, CCR4+CCR6−, CXCR3+CCR6+, and CXCR3+CCR6− T cells expressed cytokines and transcription factors specific for Th17, Th2, Th1Th17, and Th1 lineages, respectively. CCR4+CCR6+ and CXCR3+CCR6+ T cells expressed the HIV coreceptors CCR5 and CXCR4 and were permissive to R5 and X4 HIV replication. CCR4+CCR6− T cells expressed CXCR4 but not CCR5 and were permissive to X4 HIV only. CXCR3+CCR6− T cells expressed CCR5 and CXCR4 but were relatively resistant to R5 and X4 HIV in vitro. Total CCR6+ T cells compared with CCR6− T cells harbored higher levels of integrated HIV DNA in treatment-naive HIV-infected subjects. The frequency of total CCR6+ T cells and those of CCR4+CCR6+ and CXCR3+CCR6+ T cells were diminished in chronically infected HIV-positive subjects, despite viral-suppressive therapy. A high-throughput analysis of cytokine profiles identified CXCR3+CCR6+ T cells as a major source of TNF-α and CCL20 and demonstrated a decreased TNF-α/IL-10 ratio in CXCR3+CCR6− T cells. Finally, CCR4+CCR6+ and CXCR3+CCR6+ T cells exhibited gut- and lymph node-homing potential. Thus, we identified CCR4+CCR6+ and CXCR3+CCR6+ T cells as highly permissive to HIV replication, with potential to infiltrate and recruit more CCR6+ T cells into anatomic sites of viral replication. It is necessary that new therapeutic strategies against HIV interfere with viral replication/persistence in discrete CCR6+ T cell subsets.
IL-33 Induces IL-13–Dependent Cutaneous Fibrosis
Authors: Rankin Andrew L. , Mumm John B. , Murphy Erin , Turner Scott , Yu Ni , McClanahan Terrill K. , Bourne Patricia A. , Pierce Robert H. , Kastelein Rob , Pflanz Stefan 
Published: December 2009

Abstract
IL-33 is constitutively expressed in epithelial barrier tissues, such as skin. Although increased expression of IL-33/IL-33R has been correlated with fibrotic disorders, such as scleroderma and progressive systemic sclerosis, the direct consequences of IL-33 release in skin has not been reported. To determine the effects of dysregulated IL-33 signaling in skin, we administered IL-33 s.c. and monitored its effects at the injection site. Administration of IL-33 resulted in IL-33R–dependent accumulation of eosinophils, CD3+ lymphocytes, F4/80+ mononuclear cells, increased expression of IL-13 mRNA, and the development of cutaneous fibrosis. Consistent with extensive cutaneous tissue remodeling, IL-33 resulted in significant modulation of a number of extracellular matrix-associated genes, including collagen VI, collagen III, and tissue inhibitor of metalloproteases-1. We establish that IL-33–induced fibrosis requires IL-13 using IL-13 knockout mice and eosinophils using ΔdblGATA mice. We show that bone marrow-derived eosinophils secrete IL-13 in response to IL-33 stimulation, suggesting that eosinophil-derived IL-13 may promote IL-33–induced cutaneous fibrosis. Collectively, our results identify IL-33 as a previously unrecognized profibrotic mediator in skin and highlight the cellular and molecular pathways by which this pathology develops.