bluuebunny/crossref_metadata_2025_split huggingface dataset:
Acute renal disease fromLeptospira interrogansin three yearlings from the same farm
Authors: Frellstedt L. , Slovis N. M. 
Published: August 2009

SummaryRenal dysfunction due to leptospirosis has been reported infrequently in the horse. The animals in this case presentation developed an acute and persistent febrile illness that could have been attributed to a number of infectious diseases. Upon numerous subsequent clinical evaluations, detection of renal dysfunction narrowed the list of differential diagnoses.This Case Report describes 3 horses with acute renal disease fromLeptospira interrogans. Pyrexia was the initial clinical sign and was refractory to antimicrobial therapy. Once azotaemia developed, leptospirosis was diagnosed as the origin of the renal dysfunction. Treatment included i.v. crystalloid fluids, diuretics, anti‐inflammatory medication, antibiotics, pentoxifylline and polysulphated glucosaminoglycan. Additionally, one of these 3 horses required a continuous infusion of vasopressors to resolve the azotaemia. Pyrexia resolved within 48 h of treatment initiation for leptospirosis. The azotaemia resolved completely after 3 months (Case 1), 3 weeks (Case 2) and 5 days (Case 3).
Interstitial brachytherapy in the management of haemangiosarcoma of the rostrum of the horse: Case report and review of the literature
Authors: Burks B. S. , Leonard J. M. , Orsini J. A. , Trombetta M. 
Published: August 2009

SummarySarcomas arising in the equine species are rare tumours, and treatment is generally surgical. Radiotherapy has been used in the management of malignancies of large animals; however, conventional external radiotherapy delivery is difficult. Interstitial brachytherapy has been used in the management of human sarcomas with reasonable success, although equine experience is minimal. We report a case of equine haemangiosarcoma treated with brachytherapy demonstrating the feasibility of the procedure and the highly malignant natural history of haemangiosarcoma.An 8‐year‐old American Saddlebred gelding presented for evaluation of a soft tissue mass on the forehead which had been present for at least 6 months. Initial surgical attempts at management were unsuccessful; therefore a radiation oncologist specialising in brachytherapy was consulted. The radiation oncologist and veterinary surgeon performed an interstitial implant of the tumour mass on the rostrum of the horse under general anaesthesia. The procedure was well tolerated by the horse. The tumour demonstrated immediate response and was noted to have completely regressed within 6 weeks of the implant removal. Unfortunately, the horse developed widespread metastatic disease and required euthanasia. At the time of necropsy, no visible tumour was identified at the implant site.Interstitial brachytherapy is feasible in soft tissue sarcomas of the horse; however, supportive demands are great with this procedure and we recommend it only be done at large speciality centres.
Surgical management of a pony with a traumatic medial luxation of the patella
Authors: O'Meara B. , Lischer C. J. 
Published: August 2009

SummaryThis report describes a successful surgical repair of medial patellar luxation in a Miniature Shetland pony where manual reduction of the patella was not possible. The surgical procedure involves transection of the medial femoropatellar ligament to facilitate patellar release, the placement of a prosthetic suture to replace the lateral femoropatellar ligament and reinforcement of the lateral retinaculum by the use of a mesh implant. This is a newly described surgical technique for the rare but recognised condition of a medial luxation of the patella.
The treatment of diarrhoea in the adult horse
Authors: Naylor R. J. , Dunkel B. 
Published: August 2009

SummaryThe priority in treating the equine patient with acute diarrhoea is to stabilise the haemodynamic aberrations secondary to the fluid and electrolyte losses. Once this has been initiated and the patient is stabilised ancillary treatments may be beneficial. Besides the well established effects of NSAIDs and polymixin B on systemic inflammation, recent studies suggest that the use of DTOS to bind bacterial toxins andSaccharomyces boulardiito reduce the severity and duration of diarrhoea may be beneficial. The justification for using probiotic products is scant. There is no evidence to suggest that systemic use of antimicrobials benefits equine patients with colitis, with the exception of metronidazole in cases of clostridial diarrhoea. In light of their potentially detrimental effects, their use can, in the opinion of the authors, not be advocated. Better understanding of the pathways of systemic inflammation and more selective anti‐inflammatory drugs may be of great benefit in the future.
A Novel Humanized Neonatal Autoimmune Blistering Skin Disease Model Induced by Maternally Transferred Antibodies
Authors: Nishie Wataru , Sawamura Daisuke , Natsuga Ken , Shinkuma Satoru , Goto Maki , Shibaki Akihiko , Ujiie Hideyuki , Olasz Edit , Yancey Kim B. , Shimizu Hiroshi 
Published: August 2009

Abstract
All mammal neonates receive maternal Abs for protection against pathogenic organisms in the postnatal environment. However, neonates can experience serious adverse reactions if the Abs transferred from the mother recognize self-molecules as autoAgs. In this study, we describe a novel model for autoimmune disease induced by transferred maternal Abs in genetically transformed Ag-humanized mice progeny. Bullous pemphigoid is the most common life-threatening autoimmune blistering skin disease that affects the elderly, in which circulating IgG autoAbs are directed against epidermal type XVII collagen (COL17). We have established a genetically manipulated experimental mouse model in which maternal Abs against human COL17 are transferred to pups whose skin expresses only human and not mouse COL17, resulting in blistering similar to that seen in patients with bullous pemphigoid. Maternal transfer of pathogenic Abs to humanized neonatal mice is a unique and potential experimental system to establish a novel autoimmune disease model.
Inflammatory Role of ASC in Antigen-Induced Arthritis Is Independent of Caspase-1, NALP-3, and IPAF
Authors: Kolly Laeticia , Karababa Mahir , Joosten Leo A. B. , Narayan Sharmal , Salvi Roberto , Pétrilli Virginie , Tschopp Jurg , van den Berg Wim B. , So Alexander Kai-Lik , Busso Nathalie 
Published: August 2009

AbstractBecause IL-1β plays an important role in inflammation in human and murine arthritis, we investigated the contribution of the inflammasome components ASC, NALP-3, IPAF, and caspase-1 to inflammatory arthritis. We first studied the phenotype of ASC-deficient and wild-type mice during Ag-induced arthritis (AIA). ASC−/− mice showed reduced severity of AIA, decreased levels of synovial IL-1β, and diminished serum amyloid A levels. In contrast, mice deficient in NALP-3, IPAF, or caspase-1 did not show any alteration of joint inflammation, thus indicating that ASC associated effects on AIA are independent of the classical NALP-3 or IPAF inflammasomes. Because ASC is a ubiquitous cytoplasmic protein that has been implicated in multiple cellular processes, we explored other pathways through which ASC may modulate inflammation. Ag-specific proliferation of lymph node and spleen cells from ASC-deficient mice was significantly decreased in vitro, as was the production of IFN-γ, whereas IL-10 production was enhanced. TCR ligation by anti-CD3 Abs in the presence or absence of anti-CD28 Abs induced a reduction in T cell proliferation in ASC−/− T cells compared with wild-type ones. In vivo lymph node cell proliferation was also significantly decreased in ASC−/− mice, but no effects on apoptosis were observed either in vitro or in vivo in these mice. In conclusion, these results strongly suggest that ASC modulates joint inflammation in AIA through its effects on cell-mediated immune responses but not via its implication in inflammasome formation.
Persistent Viral Infection Elevates Central Nervous System MHC Class I through Chronic Production of Interferons
Authors: Truong Phi , Heydari Sara , Garidou Lucile , McGavern Dorian B. 
Published: August 2009

Abstract
Persistence of even the stealthiest viruses can perturb immune function either to the benefit or detriment of the host. Lymphocytic choriomeningitis virus (LCMV) establishes lifelong, systemic persistence when introduced in utero or at birth. Despite a highly evolved host-pathogen relationship, LCMV cannot escape detection by the innate immune system, which results in chronic stimulation of the type 1 IFN pathway in adult carrier mice. In this study we demonstrate that IFN-β is chronically up-regulated in peripheral lymphoid and nonlymphoid tissues (but not the CNS) of mice persistently infected from birth with LCMV and that dendritic cells (DCs) represent at least one source of IFN-β. Interestingly, chronic stimulation of this innate pathway significantly elevated MHC class I expression in the CNS as well as the periphery. Elevated MHC I expression was dependent on IFN-αβ receptor but not MyD88-dependent signaling, as only genetic deletion of the former reduced MHC I to normal levels. An increase in circulating virus was also observed in the IFN-αβ receptor deficient carrier mice, signifying that type I IFN continually exerts anti-viral pressure during a LCMV carrier state. Finally, to determine whether heightened CNS MHC I could be therapeutically corrected, we purged LCMV carrier mice of their persistent infection using adoptive immunotherapy. This treatment significantly reduced CNS MHC I expression. Collectively, these data demonstrate that even a well adapted pathogen can chronically stimulate the innate immune system and consequently alter the expression of Ag presenting machinery in an immunologically specialized compartment like the CNS.
Expression of IgM, IgD, and IgY in a Reptile, Anolis carolinensis
Authors: Wei Zhiguo , Wu Qian , Ren Liming , Hu Xiaoxiang , Guo Ying , Warr Gregory W. , Hammarström Lennart , Li Ning , Zhao Yaofeng 
Published: August 2009

Abstract
The reptiles are the last major group of jawed vertebrates in which the organization of the IGH locus and its encoded Ig H chain isotypes have not been well characterized. In this study, we show that the green anole lizard (Anolis carolinensis) expresses three Ig H chain isotypes (IgM, IgD, and IgY) but no IgA. The presence of the δ gene in the lizard demonstrates an evolutionary continuity of IgD from fishes to mammals. Although the germline δ gene contains 11 CH exons, only the first 4 are used in the expressed IgD membrane-bound form. The μ chain lacks the cysteine in CH1 that forms a disulfide bond between H and L chains, suggesting that (as in IgM of some amphibians) the H and L polypeptide chains are not covalently associated. Although conventional IgM transcripts (four CH domains) encoding both secreted and membrane-bound forms were detected, alternatively spliced transcripts encoding a short membrane-bound form were also observed and shown to lack the first two CH domains (VDJ-CH3-CH4-transmembrane region). Similar to duck IgY, lizard IgY H chain (υ) transcripts encoding both full-length and truncated (IgYΔFc) forms (with two CH domains) were observed. The absence of an IgA-encoding gene in the lizard IGH locus suggests a complex evolutionary history for IgA in the saurian lineage leading to modern birds, lizards, and their relatives.
Externalization of the Leaderless Cytokine IL-1F6 Occurs in Response to Lipopolysaccharide/ATP Activation of Transduced Bone Marrow Macrophages
Authors: Martin Unja , Scholler John , Gurgel Jesse , Renshaw Blair , Sims John E. , Gabel Christopher A. 
Published: August 2009

AbstractAn interesting trait shared by many members of the IL-1 cytokine family is the absence of a signal sequence that can direct the newly synthesized polypeptides to the endoplasmic reticulum. As a result, these cytokines accumulate intracellularly. Recent studies investigating IL-1β export established that its release is facilitated via activation of an intracellular multiprotein complex termed the inflammasome. The purpose of the current study was to explore the mechanism by which murine IL-1F6 is released from bone marrow-derived macrophages (BMDMs) and to compare this mechanism to that used by IL-1β. BMDMs were engineered to overexpress IL-1F6 by retroviral transduction; cells overexpressing GFP also were generated to provide a noncytokine comparator. The transduced cells constitutively expressed IL-1F6 and GFP, but they did not constitutively release these polypeptides to the medium. Enhanced release of IL-1F6 was achieved by treating with LPS followed by ATP-induced activation of the P2X7 receptor; GFP also was released under these conditions. No obvious proteolytic cleavage of IL-1F6 was noted following P2X7 receptor-induced release. Stimulus-induced release of IL-1F6 and GFP demonstrated comparable susceptibility to pharmacological modulation. Therefore, transduced IL-1F6 is released in parallel with endogenous mature IL-1β from LPS/ATP-treated BMDMs, but this externalization process is not selective for cytokines as a noncytokine (GFP) shows similar behavior. These findings suggest that IL-1F6 can be externalized via a stimulus-coupled mechanism comparable to that used by IL-1β, and they provide additional insight into the complex cellular processes controlling posttranslational processing of the IL-1 cytokine family.
Eosinophil Ribonucleases and Their Cutaneous Lesion-Forming Activity
Authors: Plager Douglas A. , Davis Mark D. P. , Andrews Amy G. , Coenen Michael J. , George Terry J. , Gleich Gerald J. , Leiferman Kristin M. 
Published: August 2009

Abstract
Eosinophil granule proteins are deposited in cutaneous lesions in many human diseases, but how these proteins contribute to pathophysiology is obscure. We injected eosinophil cationic protein (ECP or RNase 3), eosinophil-derived neurotoxin (EDN or RNase 2), eosinophil peroxidase (EPO), and major basic protein-1 (MBP1) intradermally into guinea pig and rabbit skin. ECP and EDN each induced distinct skin lesions at ≥2.5 μM that began at 2 days, peaking at ∼7 days and persisting up to 6 wk. These lesions were ulcerated (ECP) or crusted (EDN) with marked cellular infiltration. EPO and MBP1 (10 μM) each produced perceptible induration and erythema with moderate cellular infiltration resolving within 2 wk. ECP and EDN localized to dermal cells within 2 days, whereas EPO and MBP1 remained extracellular. Overall, cellular localization and RNase activity of ECP and EDN were critical for lesion formation; differential glycosylation, net cationic charge, or RNase activity alone did not account for lesion formation. Ulcerated lesions from patients with the hypereosinophilic syndrome showed ECP and EDN deposition comparable to that in guinea pig skin. In conclusion, ECP and EDN disrupt skin integrity and cause inflammation. Their presence in ulcerative skin lesions may explain certain findings in human eosinophil-associated diseases.
Cutting Edge: Stealth Influenza Virus Replication Precedes the Initiation of Adaptive Immunity
Authors: Moltedo Bruno , López Carolina B. , Pazos Michael , Becker María Inés , Hermesh Tamar , Moran Thomas M. 
Published: August 2009

Abstract
A timely immune response is crucial for the effective control of virus infection. The influenza virus NS1 protein interferes with the expression of key proinflammatory cytokines from infected cells in vitro. To investigate the effect of NS1 during the onset of immunity in vivo, we systematically studied the early events that occur in the lungs and draining lymph nodes upon infection with influenza virus. Strikingly, no sign of innate immunity was detected in the lungs for almost 2 days after infection until a sudden inflammatory burst, including IFNs, cytokines, and chemokines, occurred. This burst preceded the robust dendritic cell migration and T cell activation in the lymph nodes. An NS1-deficient virus triggered rapid inflammation in the lungs whereas a wild-type virus did not. Thus, we demonstrate that, in vivo, influenza virus uses the NS1 protein to replicate for almost 2 days after infection before detection by the immune system.
Site-Specific Carboxypeptidase B1 Tyrosine Nitration and Pathophysiological Implications following Its Physical Association with Nitric Oxide Synthase-3 in Experimental Sepsis
Authors: Chatterjee Saurabh , Lardinois Olivier , Bonini Marcelo G. , Bhattacharjee Suchandra , Stadler Krisztian , Corbett Jean , Deterding Leesa J. , Tomer Kenneth B. , Kadiiska Maria , Mason Ronald P. 
Published: August 2009

Abstract
LPS-induced sepsis results in oxidative modification and inactivation of carboxypeptidase B1 (CPB1). In this study, immunoprecipitated CPB1 was probed for tyrosine nitration using monoclonal nitrotyrosine-specific Abs in a murine model of LPS-induced sepsis. Tyrosine nitration of CPB1 was significantly reduced in the presence of NO synthase (NOS) inhibitors and the xanthine oxidase (XO) inhibitor allopurinol and in NOS-3 knockout (KO) mice. CPB1 tyrosine nitration and loss of activity by the concerted action of NOS-3 and XO were also confirmed in vitro using both the NO donor 3-morpholinosydnonimine and peroxynitrite. Liquid chromatography/tandem mass spectrometry data indicated five sites of tyrosine nitration in vitro including Tyr248, the tyrosine at the catalytic site. The site- and protein-specific nitration of CPB1 and the possible high nitration yield to inactivate it were elucidated by confocal microscopy. The studies indicated that CPB1 colocalized with NOS-3 in the cytosol of sinus-lining cells in the red pulp of the spleen. Further analysis of CPB1-immunoprecipitated samples indicated immunoreactivity to a monoclonal NOS-3 Ab, suggesting protein complex formation with CPB1. XO and NOS inhibitors and NOS-3 KO mice injected with LPS had decreased levels of C5a in spleens of septic mice, indicating peroxynitrite as a possible cause for CPB1 functional alteration. Thus, CPB1 colocalization, coupling, and proximity to NOS-3 in the sinus-lining cells of spleen red pulp could explain the site-specific tyrosine nitration and inactivation of CPB1. These results open up new avenues for the investigation of several enzymes involved in inflammation and their site-specific oxidative modifications by protein-protein interactions as well as their role in sepsis.
A Critical Role for Hemolysins and Bacterial Lipoproteins in Staphylococcus aureus-Induced Activation of the Nlrp3 Inflammasome
Authors: Muñoz-Planillo Raúl , Franchi Luigi , Miller Lloyd S. , Núñez Gabriel 
Published: August 2009

Abstract
The mechanism by which bacterial pathogens activate caspase-1 via Nlrp3 remains poorly understood. In this study, we show that the ability of Staphylococcus aureus, a leading cause of infection in humans, to activate caspase-1 and induce IL-1β secretion resides in culture supernatants of growing bacteria. Caspase-1 activation induced by S. aureus required α-, β-, and γ-hemolysins and the host Nlrp3 inflammasome. Mechanistically, α- and β-hemolysins alone did not trigger caspase-1 activation, but they did so in the presence of bacterial lipoproteins released by S. aureus. Notably, caspase-1 activation induced by S. aureus supernatant was independent of the P2X7 receptor and the essential TLR adaptors MyD88 and TIR domain-containing adapter-inducing IFN-β, but was inhibited by extracellular K+. These results indicate that S. aureus hemolysins circumvent the requirement of ATP and the P2X7 receptor to induce caspase-1 activation via Nlrp3. Furthermore, these studies revealed that hemolysins promote in the presence of lipoproteins the activation of the Nlrp3 inflammasome.
De Novo Generation and Enhanced Suppression of Human CD4+CD25+ Regulatory T Cells by Retinoic Acid
Authors: Wang Jun , Huizinga Tom W. J. , Toes Rene E. M. 
Published: August 2009

Abstract
Therapies based on CD4+CD25+FOXP3+ T regulatory (Treg) cells offer promise for the restoration of tolerance in many immune-mediated disorders. However, it has been proven difficult to obtain large numbers of Treg cells with potent and stable suppressive ability from adult human peripheral blood because of the lack of specific markers for Treg isolation/characterization, compromised function of isolated CD4+CD25+/+ T cell populations, and the difficulty to convert conventional T cells, for example, by TGF-β, into Treg cells in a consistent manner. In this study, we show that 1) in the presence of TGF-β, all-trans-retinoic acid (ATRA) efficiently converts adult human peripheral blood naive CD4+ T cells into FOXP3+ Treg cells with stable and potent suppressive ability; 2) memory CD4+ T cells are resistant to FOXP3 induction and, moreover, inhibit Treg conversion of naive T cells that can be partially reversed by anti-IL-4; and 3) treatment of isolated CD4+CD25+/+ T cells with ATRA/TGF-β enhances their suppressive potential during expansion. Our results indicate that ATRA/TGF-β can be used to generate highly suppressive CD4+FOXP3+ Treg cells from adult human peripheral blood and are relevant for the development for Treg-based therapies.
β-Catenin/Tcf Determines the Outcome of Thymic Selection in Response to αβTCR Signaling
Authors: Kovalovsky Damian , Yu Yu , Dose Marei , Emmanouilidou Anastasia , Konstantinou Tassos , Germar Kristine , Aghajani Katayoun , Guo Zhuyan , Mandal Malay , Gounari Fotini 
Published: August 2009

Abstract
Thymic maturation of T cells depends on the intracellular interpretation of αβTCR signals by processes that are poorly understood. In this study, we report that β-catenin/Tcf signaling was activated in double-positive thymocytes in response to αβTCR engagement and impacted thymocyte selection. TCR engagement combined with activation of β-catenin signaled thymocyte deletion, whereas Tcf-1 deficiency rescued from negative selection. Survival/apoptotis mediators including Bim, Bcl-2, and Bcl-xL were alternatively influenced by stabilization of β-catenin or ablation of Tcf-1, and Bim-mediated β-catenin induced thymocyte deletion. TCR activation in double-positive cells with stabilized β-catenin triggered signaling associated with negative selection, including sustained overactivation of Lat and Jnk and a transient activation of Erk. These observations are consistent with β-catenin/Tcf signaling acting as a switch that determines the outcome of thymic selection downstream the αβTCR cascade.
The Two Groups of Zebrafish Virus-Induced Interferons Signal via Distinct Receptors with Specific and Shared Chains
Authors: Aggad Dina , Mazel Martine , Boudinot Pierre , Mogensen Knud Erik , Hamming Ole Jensen , Hartmann Rune , Kotenko Sergei , Herbomel Philippe , Lutfalla Georges , Levraud Jean-Pierre 
Published: August 2009

Abstract
Because the availability of fish genomic data, the number of reported sequences for fish type II helical cytokines is rapidly growing, featuring different IFNs including virus-induced IFNs (IFNφ) and IFN-γ, and IL-10 with its related cytokines (IL-20, IL-22, and IL-26). Many candidate receptors exist for these cytokines and various authors have postulated which receptor chain would be involved in which functional receptor in fish. To date, only the receptor for zebrafish IFNφ1 has been identified functionally. Three genes encoding virus-induced IFNφs have been reported in zebrafish. In addition to these genes clustered on chromosome 3, we have identified a fourth IFNφ gene on chromosome 12. All these genes possess the intron-exon organization of mammalian λ IFNs. In the zebrafish larva, all induce the expression of reporter antiviral genes; protection in a viral challenge assay was observed for IFNφ1 and IFNφ2. Using a combination of gain- and loss-of-function experiments, we also show that all zebrafish IFNφs do not bind to the same receptor. Two subgroups of fish virus-induced IFNs have been defined based on conserved cysteines, and we find that this subdivision correlates with receptor usage. Both receptor complexes include a common short chain receptor (CRFB5) and a specific long chain receptor (CRFB1 or CRFB2).