bluuebunny/crossref_metadata_2025_split huggingface dataset:
Simultaneous Measurement of Antigen-Stimulated Interleukin-1β and Gamma Interferon Production Enhances Test Sensitivity for the Detection of
Mycobacterium bovis
Infection in Cattle
Authors: Jones Gareth J. , Pirson Chris , Hewinson R. Glyn , Vordermeier H. Martin 
Published: October 2010

ABSTRACT

In order to identify cytokines that may be useful as candidates for inclusion in diagnostic tests for
Mycobacterium bovis
infection in cattle, we compared the levels of gamma interferon (IFN-γ), interleukin 1β (IL-1β), IL-4, IL-10, IL-12, macrophage inflammatory protein 1β (MIP-1β), and tumor necrosis factor alpha (TNF-α) in whole-blood cultures from tuberculosis (TB) reactor animals or TB-free controls following stimulation with
M. bovis
-specific antigens (purified protein derivative from
M
.
bovis
[PPD-B] or ESAT-6/CFP-10). In addition to IFN-γ responses, the production of IL-1β and TNF-α was also statistically significantly elevated in TB reactor cattle over that in uninfected controls following stimulation with PPD-B or ESAT-6/CFP-10 peptides. Thus, we evaluated whether the use of these two additional readouts could disclose further animals not detected by measuring IFN-γ alone. To this end, receiver operating characteristic (ROC) analyses were performed to define diagnostic cutoffs for positivity for TNF-α and IL-1β. These results revealed that for ESAT-6/CFP-10-induced responses, the use of all three readouts (IFN-γ, TNF-α, and IL-1β) in parallel increased the sensitivity of detection of
M. bovis
-infected animals by 11% but also resulted in a specificity decrease of 14%. However, applying only IFN-γ and IL-1β in parallel resulted in a 5% increase in sensitivity without the corresponding loss of specificity. The results for PPD-B-induced responses were similar, although the loss of specificity was more pronounced, even when only IFN-γ and IL-1β were used as readout systems. In conclusion, we have demonstrated that the use of an additional readout system, such as IL-1β, can potentially complement IFN-γ by increasing overall test sensitivity for the detection of
M. bovis
infection in cattle.
Detection of a Novel Astrovirus in Brain Tissue of Mink Suffering from Shaking Mink Syndrome by Use of Viral Metagenomics
Authors: Blomström Anne-Lie , Widén Frederik , Hammer Anne-Sofie , Belák Sándor , Berg Mikael 
Published: October 2010

ABSTRACT
In 2000, farmed mink kits in Denmark were affected by a neurological disorder. The characteristic clinical signs included shaking, staggering gait, and ataxia. The disease, given the name shaking mink syndrome, was reproduced by the inoculation of brain homogenate from affected mink kits into healthy ones. However, the etiology remained unknown despite intensive efforts. In this study, random amplification and large-scale sequencing were used, and an astrovirus was detected in the brain tissue of three experimentally infected mink kits. This virus also was found in the brain of three mink kits naturally displaying the disease but not in the six healthy animals investigated. The complete coding region of the detected astrovirus was sequenced and compared to those of both a mink astrovirus associated with preweaning diarrhea and to a recently discovered human astrovirus associated with a case of encephalitis in a boy with x-linked agammaglobulinemia. The identities were 80.4 and 52.3%, respectively, showing that the virus described in this study was more similar to the preweaning diarrhea mink astrovirus. For the nonstructural coding regions the sequence identity was around 90% compared to that of the astrovirus, which is associated with preweaning diarrhea in mink. The region coding for the structural protein was more diverse, showing only 67% sequence identity. This finding is of interest not only because the detected virus may be the etiological agent of the shaking mink syndrome but also because this is one of the first descriptions of an astrovirus found in the central nervous system of animals.
Normalized Resistance Interpretation as a Tool for Establishing Epidemiological MIC Susceptibility Breakpoints
Authors: Kronvall Göran 
Published: October 2010

ABSTRACT

Normalized resistance interpretation (NRI) utilizes the fact that the wild-type population on the sensitive side is not affected by resistance development, and therefore a normalized reconstruction of the peak can be performed. The method was modified for MIC distributions by the introduction of helper variables, in-between values assigned the mean of the neighboring numbers of isolates. This method was used on
Staphylo- coccus aureus
and
Escherichia coli
MIC distributions for 27 antimicrobials each and obtained from the EUCAST (European Committee on Antimicrobial Susceptibility Testing) website (
http://www.eucast.org/mic_distributions/
). The number of isolates in each of the 54 distributions ranged from 40 to 124,472. NRI produced normalized distributions in all cases. Cutoff values were calculated for +2.0 and +2.5 standard deviations (SD) above the means and then rounded up to nearest regular MIC dilution step. EUCAST also show cutoff values, ECOFF values, which were used as the reference. The NRI generated +2.0 SD values showed the best agreement with 26 of 27 within ±1 dilution step and 17 exactly on the ECOFF values for
Staphylococcus aureus
, and 25 of 27 within ±1 dilution step and 14 right on the ECOFF values for
Escherichia coli
. NRI offers an objective method for the reconstruction of the wild-type population in an MIC distribution for a given bacterial species and an antimicrobial agent. This method offers a new tool in comparative susceptibility studies such as global surveillance of resistance, as well as in quality control in individual laboratories.
Histoplasma capsulatum
Prosthetic Valve Endocarditis with Negative Fungal Blood Cultures and Negative
Histoplasma
Antigen Assay in an Immunocompetent Patient
Authors: Jinno Sadao , Gripshover Barbara M. , Lemonovich Tracy L. , Anderson James M. , Jacobs Michael R. 
Published: October 2010

ABSTRACT

We report a case of
Histoplasma capsulatum
endocarditis in which
Histoplasma
antigen assay and fungal blood cultures were negative. The diagnosis was made by microscopic examination and culture of the excised valve.
Histoplasma capsulatum
should be considered in the differential diagnosis of culture-negative endocarditis in regions where it is endemic and in travelers.
Metagenomic Analysis of the Viromes of Three North American Bat Species: Viral Diversity among Different Bat Species That Share a Common Habitat
Authors: Donaldson Eric F. , Haskew Aimee N. , Gates J. Edward , Huynh Jeremy , Moore Clea J. , Frieman Matthew B. 
Published: October 2010

ABSTRACTEffective prediction of future viral zoonoses requires an in-depth understanding of the heterologous viral population in key animal species that will likely serve as reservoir hosts or intermediates during the next viral epidemic. The importance of bats as natural hosts for several important viral zoonoses, including Ebola, Marburg, Nipah, Hendra, and rabies viruses and severe acute respiratory syndrome-coronavirus (SARS-CoV), has been established; however, the large viral population diversity (virome) of bats has been partially determined for only a few of the ∼1,200 bat species. To assess the virome of North American bats, we collected fecal, oral, urine, and tissue samples from individual bats captured at an abandoned railroad tunnel in Maryland that is cohabitated by 7 to 10 different bat species. Here, we present preliminary characterization of the virome of three common North American bat species, including big brown bats (Eptesicus fuscus), tricolored bats (Perimyotis subflavus), and little brown myotis (Myotis lucifugus). In samples derived from these bats, we identified viral sequences that were similar to at least three novel group 1 CoVs, large numbers of insect and plant virus sequences, and nearly full-length genomic sequences of two novel bacteriophages. These observations suggest that bats encounter and disseminate a large assortment of viruses capable of infecting many different animals, insects, and plants in nature.
Transforming Growth Factor Beta Is a Major Regulator of Human Neonatal Immune Responses following Respiratory Syncytial Virus Infection
Authors: Thornburg Natalie J. , Shepherd Bryan , Crowe James E. 
Published: October 2010

ABSTRACTRespiratory syncytial virus (RSV) is a major cause of morbidity and mortality. Previous studies have suggested that T-cell responses may contribute to RSV immunopathology, which could be driven by dendritic cells (DCs). DCs are productively infected by RSV, and during RSV infections, there is an increase of DCs in the lungs with a decrease in the blood. Pediatric populations are particularly susceptible to severe RSV infections; however, DC responses to RSV from pediatric populations have not been examined. In this study, primary isolated DCs from cord blood and adult peripheral blood were compared after RSV infection. Transcriptional profiling and biological network analysis identified transforming growth factor beta (TGF-β) and associated signaling molecules as differentially regulated in the two age groups. TGF-β1 was decreased in RSV-infected adult-blood DCs but increased in RSV-infected cord blood DCs. Coculture of adult RSV-infected DCs with autologous T cells induced secretion of gamma interferon (IFN-γ), interleukin 12p70 (IL-12p70), IL-2, and tumor necrosis factor alpha (TNF-α). Conversely, coculture of cord RSV-infected DCs and autologous T cells induced secretion of IL-4, IL-6, IL-1β, and IL-17. Addition of purified TGF-β1 to adult DC-T-cell cocultures reduced secretion of IFN-γ, IL-12p70, IL-2, and TNF-α, while addition of a TGF-β chemical inhibitor to cord DC-T-cell cocultures increased secretion of IL-12p70. These data suggest that TGF-β acts as a major regulator of RSV DC-T-cell responses, which could contribute to immunopathology during infancy.
Mice Lacking Alpha/Beta and Gamma Interferon Receptors Are Susceptible to Junin Virus Infection
Authors: Kolokoltsova Olga A. , Yun Nadezda E. , Poussard Allison L. , Smith Jennifer K. , Smith Jeanon N. , Salazar Milagros , Walker Aida , Tseng Chien-Te K. , Aronson Judith F. , Paessler Slobodan 
Published: October 2010

ABSTRACT

Junin virus (JUNV) causes a highly lethal human disease, Argentine hemorrhagic fever. Previous work has demonstrated the requirement for human transferrin receptor 1 for virus entry, and the absence of the receptor was proposed to be a major cause for the resistance of laboratory mice to JUNV infection. In this study, we present for the first time
in vivo
evidence that the disruption of interferon signaling is sufficient to generate a disease-susceptible mouse model for JUNV infection. After peripheral inoculation with virulent JUNV, adult mice lacking alpha/beta and gamma interferon receptors developed disseminated infection and severe disease.
Determinants of Tetherin Antagonism in the Transmembrane Domain of the Human Immunodeficiency Virus Type 1 Vpu Protein
Authors: Vigan Raphaël , Neil Stuart J. D. 
Published: October 2010

ABSTRACTTetherin (BST2/CD317) potently restricts the particle release of human immunodeficiency virus type 1 (HIV-1) mutants defective in the accessory genevpu. Vpu antagonizes tetherin activity and induces its cell surface downregulation and degradation in a manner dependent on the transmembrane (TM) domains of both proteins. We have carried out extensive mutagenesis of the HIV-1 NL4.3 Vpu TM domain to identify three amino acid positions, A14, W22, and, to a lesser extent, A18, that are required for tetherin antagonism. Despite the mutants localizing indistinguishably from the wild-type (wt) protein and maintaining the ability to multimerize, mutation of these positions rendered Vpu incapable of coimmunoprecipitating tetherin or mediating its cell surface downregulation. Interestingly, these amino acid positions are predicted to form one face of the Vpu transmembrane alpha helix and therefore potentially contribute to an interacting surface with the transmembrane domain of tetherin either directly or by modulating the conformation of Vpu oligomers. While the equivalent of W22 is invariant in HIV-1/SIVcpz Vpu proteins, the positions of A14 and A18 are highly conserved among Vpu alleles from HIV-1 groups M and N, but not those from group O or SIVcpz that lack human tetherin (huTetherin)-antagonizing activity, suggesting that they may have contributed to the adaption of HIV-1 to human tetherin.
Significant increase in IgG4+ plasma cells in gastric biopsy specimens from patients with pernicious anaemia
Authors: Bedeir Ahmed S , Lash Richard H , Lash Jonathan G , Ray Mukunda B 
Published: October 2010

AimTo investigate the presence of IgG4+ plasma cells in gastric mucosal biopsy samples from patients with atrophic gastritis (AG) and a history of pernicious anaemia (PA) (AG+PA+).MethodsGastric mucosal biopsy specimens from 46 patients with AG+PA+ were investigated. As controls, we evaluated specimens from patients with AG but no history of PA (AG+ PA–) (n=25), normal histology (n=25), mild chronic inactive gastritis (MCIG) (n=25) orHelicobacter pylorigastritis (HP) (n=25). IgG4+ plasma cells were detected by two immunohistochemical methods: (1) using a monoclonal antibody, the average of the three most cellular high-power fields was counted in areas with the highest density of IgG4+ plasma cells; (2) using a dual-chromagen stain for both IgG4 and CD138 (plasma cell marker), the number of IgG4+ cells per 200 CD138+ plasma cells was counted. The latter was used to ensure that the number of IgG4+ cells was not simply related to the degree of inflammation (density of plasma cells).ResultsIdentical results were obtained with the two staining methods. Increased numbers of IgG4+ plasma cells were present in 37% of patients with AG+PA+, but in none with AG+PA–, MCIG, HP or normal gastric biopsy results (100% specific, p=0.0001).ConclusionIgG4+ plasma cells may play a role in the pathogenesis of PA and may be a useful marker for its diagnosis.
Haemogenic endothelium in infantile haemangioma: Figure 1
Authors: Itinteang Tinte , Tan Swee T , Brasch Helen , Day Darren J 
Published: October 2010

BackgroundProliferating infantile haemangioma (IH) is a tumour of the microvasculature composed predominantly of immature endothelial cells. The origin of IH is unclear, but it has been shown to express markers of both endothelial and haematopoietic lineages, and a role for endothelial progenitor cells in the aetiology of IH has been suggested. Haemangioblasts are precursors of both endothelial and haematopoietic cells, and their characterisation has identified the expression of cell surface and intracellular proteins that collectively can be used for assigning a haemangioblast phenotype.MethodsThe authors used immunohistochemical staining to characterise the expression of primitive haematopoietic-associated proteins in proliferating IHs.Results and discussionThe authors show that the cells forming the capillary endothelium express markers associated with primitive haematopoietic cells. Additionally, many of these cells express the transcription factors brachyury and GATA-2, indicating a primitive mesodermal origin. They hypothesise that the immature capillaries in IH are derived from primitive mesodermal cells with haemangioblastic differentiation capabilities. The expression of primitive mesodermal, endothelial and haematopoietic markers by the cells forming the endothelium suggests that the immature capillaries that predominate in proliferating IH are a haemogenic endothelium phenotype, derived from haemangioblasts.
Epithelial-to-Mesenchymal Transition Promotes Tubulin Detyrosination and Microtentacles that Enhance Endothelial Engagement
Authors: Whipple Rebecca A. , Matrone Michael A. , Cho Edward H. , Balzer Eric M. , Vitolo Michele I. , Yoon Jennifer R. , Ioffe Olga B. , Tuttle Kimberly C. , Yang Jing , Martin Stuart S. 
Published: October 2010

Abstract
Epithelial-to-mesenchymal transition (EMT) is associated with increased breast tumor metastasis; however, the specific mechanisms by which EMT promotes metastasis remain somewhat unclear. Despite the importance of cytoskeletal dynamics during both EMT and metastasis, very few current studies examine the cytoskeleton of detached and circulating tumor cells. Specific posttranslational α-tubulin modifications are critical for adherent cell motility and implicated in numerous pathologies, but also remain understudied in detached cells. We report here that EMT induced through ectopic expression of Twist or Snail promotes α-tubulin detyrosination and the formation of tubulin-based microtentacles in detached HMLEs. Mechanistically, EMT downregulates the tubulin tyrosine ligase enzyme, resulting in an accumulation of detyrosinated α-tubulin (Glu-tubulin), and increases microtentacles that penetrate endothelial layers to facilitate tumor cell reattachment. Confocal microscopy shows that microtentacles are capable of penetrating the junctions between endothelial cells. Suppression of endogenous Twist in metastatic human breast tumor cells is capable of reducing both tubulin detyrosination and microtentacles. Clinical breast tumor samples display high concordance between Glu-tubulin and Twist expression levels, emphasizing the coupling between EMT and tubulin detyrosination in vivo. Coordinated elevation of Twist and Glu-tubulin at invasive tumor fronts, particularly within ductal carcinoma in situ samples, establishes that EMT-induced tubulin detyrosination occurs at the earliest stages of tumor invasion. These data support a novel model where the EMT that occurs during tumor invasion downregulates tubulin tyrosine ligase, increasing α-tubulin detyrosination and promoting microtentacles that could enhance the reattachment of circulating tumor cells to the vascular endothelium during metastasis. Cancer Res; 70(20); 8127–37. ©2010 AACR.
Mesenchymal Stromal Cells Expressing ErbB-2/neu Elicit Protective Antibreast Tumor Immunity In vivo, Which Is Paradoxically Suppressed by IFN-γ and Tumor Necrosis Factor-α Priming
Authors: Romieu-Mourez Raphaëlle , François Moïra , Abate Amanda , Boivin Marie-Noëlle , Birman Elena , Bailey Dana , Bramson Jonathan L. , Forner Kathy , Young Yoon-Kow , Medin Jeffrey A. , Galipeau Jacques 
Published: October 2010

Abstract
It is unknown whether mesenchymal stromal cells (MSC) can regulate immune responses targeting tumor autoantigens of low immunogenicity. We tested here whether immunization with MSC could break immune tolerance towards the ErbB-2/HER-2/neu tumor antigen and the effects of priming with IFN-γ and tumor necrosis factor-α (TNF-α) on this process. BALB/c– and C57BL/6-derived MSC were lentivirally transduced to express a kinase-inactive rat neu mutant (MSC/Neu). Immunization of BALB/c mice with nontreated or IFN-γ–primed allogeneic or syngeneic MSC/Neu induced similar levels of anti-neu antibody titers; however, only syngeneic MSC/Neu induced protective neu-specific CD8+ T cell responses. Compared to immunization with nontreated or IFN-γ–primed syngeneic MSC/Neu, the number of circulating neu-specific CD8+ T cells and titers of anti-neu antibodies were observed to be decreased after immunizations with IFN-γ– plus TNF-α–primed MSC/Neu. In addition, syngeneic MSC/Neu seemed more efficient than IFN-γ–primed MSC/Neu at inducing a protective therapeutic antitumor immune response resulting in the regression of transplanted neu-expressing mammary tumor cells. In vitro antigen-presenting cell assays performed with paraformaldehyde-fixed or live MSC showed that priming with IFN-γ plus TNF-α, compared to priming with IFN-γ alone, increased antigen presentation as well as the production of immunosuppressive factors. These data suggest that whereas MSC could effectively serve as antigen-presenting cells to induce immune responses aimed at tumor autoantigens, these functions are critically regulated by IFN-γ and TNF-α. Cancer Res; 70(20); 7742–7. ©2010 AACR.
Receptor Tyrosine Kinase Signaling Favors a Protumorigenic State in Breast Cancer Cells by Inhibiting the Adaptive Immune Response
Authors: Ursini-Siegel Josie , Cory Sean , Zuo Dongmei , Hardy William R. , Rexhepaj Elton , Lam Sonya , Schade Babette , Jirstrom Karin , Bjur Eva , Piccirillo Ciriaco A. , DeNardo David , Coussens Lisa M. , Brennan Donal J. , Gallagher William M. , Park Morag , Pawson Tony , Hallett Michael , Muller William J. 
Published: October 2010

Abstract
Using transgenic mouse models of breast cancer that ablate Src homology and collagen A (ShcA) expression or oncogene-coupled ShcA signaling, we previously showed that this adaptor is critical for mammary tumor onset and progression. We now provide the first evidence that ShcA regulates mammary tumorigenesis, in part, through its ability to regulate the adaptive immune response. Inactivation of ShcA signaling within tumor cells results in extensive CD4+ T-cell infiltration and induction of a humoral immune response in mammary tumors. This is associated with a robust CTL response in preneoplastic lesions that are deficient in ShcA signaling. Moreover, mammary tumor progression of ShcA-deficient hyperplasias is accelerated in a T cell–deficient background. We also uncover a clinically relevant correlation between high ShcA expression and low CTL infiltration in human breast cancers. Finally, we define a novel ShcA-regulated immune signature that functions as an independent prognostic marker of survival in human epidermal growth factor receptor 2+ and basal breast cancers. We reveal a novel role for tumor cell–derived ShcA in the establishment and maintenance of an immunosuppressive state. Cancer Res; 70(20); 7776–87. ©2010 AACR.
Serum Platelet Factor 4 Is an Independent Predictor of Survival and Venous Thromboembolism in Patients with Pancreatic Adenocarcinoma
Authors: Poruk Katherine E. , Firpo Matthew A. , Huerter Luke M. , Scaife Courtney L. , Emerson Lyska L. , Boucher Kenneth M. , Jones Kimberly A. , Mulvihill Sean J. 
Published: October 2010

Abstract
Background: Improved diagnostic, predictive, and prognostic biomarkers for pancreatic ductal adenocarcinoma (PDAC) are urgently needed. Platelet factor 4 (PF4) has been proposed as a diagnostic biomarker for PDAC. We assessed the diagnostic and prognostic potential of serum PF4 levels in PDAC patients.
Methods: Serum PF4 levels were determined by enzyme-linked immunosorbent assay in an initial cohort of 62 PDAC patients, 62 healthy control subjects, and 34 chronic pancreatitis patients. A second validation set consisted of 71 PDAC patients. Linear regression models were used to relate PF4 to class, gender, age, stage, platelet count, and diagnosis. Survival analyses were done using univariate and multivariate Cox models.
Results: In the initial cohort, serum PF4 levels distinguished PDAC from chronic pancreatitis patients (P = 0.011), but not from healthy control subjects (P = 0.624). In PDAC patients, high serum PF4 level significantly predicted decreased survival independent of all covariates examined (P &lt; 0.01). The prognostic relationship of serum PF4 levels remained significant in the validation set. Venous thromboembolism (VTE) occurred in 20% of the 133 PDAC patients. The VTE risk was higher in subjects with elevated PF4 levels (P = 0.009).
Conclusions: Serum PF4 is shown for the first time to be prognostic for survival in PDAC patients. High PF4 is associated with an increased risk for the development of VTE.
Impact: Serum PF4 levels may be useful for patient stratification and for directing treatment options in patients with pancreatic cancer including anticoagulation prophylaxis. The relationship between high PF4 levels and poorer outcomes requires further study. Cancer Epidemiol Biomarkers Prev; 19(10); 2605–10. ©2010 AACR.