tbuckley/cabot-search huggingface dataset:
Pathogenicity of memory Th2 cells is linked to stage of allergic rhinitis
Authors: T. Iinuma, Y. Okamoto, Y. Morimoto, T. Arai, T. Sakurai, S. Yonekura, D. Sakurai, K. Hirahara, T. Nakayama
Journal: Allergy (2017)

Abstract Background Allergic rhinitis ( AR ) consists of three developmental stages that are based on the presence/absence of antigen‐specific IgE and symptoms. The pathogenic Th2 (Tpath2) cells constitute a population of Th2 cells with additional potentially pathogenic characteristics. We examined the relationship between Tpath2 cells and the stages of allergic rhinitis by focusing on ST 2, which is an IL ‐33 receptor. Methods Patients with Japanese cedar pollen‐induced AR ( JCP ‐ AR ) and healthy volunteers were divided into “nonsensitized,” “asymptomatic sensitized ( AS ),” and “ JCP ‐ AR ” groups. We analyzed the ST 2 expression and the Th2 function of cultured CD 4 + T cells. Next, we observed the progress of patients in the AS stage around the time of seasonal pollen dispersal, with the characteristics of Th2 cells. Results The ST 2 expression of T cells was only upregulated in the AR group. The production of IL ‐4 and IL ‐13 was found in CD 4 + T cells obtained from AS by stimulation with JCP , but reactivity to IL ‐33 was not observed. Although IL ‐33 did not induce the elevation of IL ‐4 production in the JCP ‐ AR group, IL ‐33 substantially increased the production of IL ‐5 and IL ‐13 in comparison with antigen stimulation alone. In newly afflicted patients, the increased expression of ST 2 and elevated reactivity to IL ‐33 was observed, even before the pollen dispersal season. Conclusions Our study demonstrated that the pathogenicity of memory Th2 cells is linked to sensitization and the stage of allergic rhinitis. Therefore, Tpath2 cells may provide useful insights into the mechanism of the onset and progression of allergic rhinitis.
Characterization of <i>KIAA1549:BRAF</i> fusion in young pilocytic astrocytoma patients through fluorescence in situ hybridization.
Authors: Marileila Varella-Garcia, Aline Paixão Becker, Jamie Sheren, Cristovam Scapulatempo Neto, Dara Aisner, Lucas Bidinotto, Luciano Neder, Chris Jones, Rui Manuel Reis
Journal: Journal of Clinical Oncology (2014)

10067 Background: Pilocytic astrocytoma (PA) often arises in young patients and may be related to type 1 neurofibromatosis (NF1). Although the 5-year survival is high, up to 10% of cases progress poorly. Alterations of BRAF mainly through gene fusions are key genetic events in this tumor type, and are reported to influence patient outcome. Our aim was to assess BRAF molecular changes in PAs for both p.V600E mutation and KIAA1549:BRAF (K:B) fusion and correlate with clinicopathological features in retrospective studies. Methods: Sanger sequencing was used to evaluate BRAF V600E mutation. K:B fusion was evaluated by a customized dual-target, dual-color fluorescence in situ hybridization (FISH) probe set in samples in tissue microarray format. The designed K:BFISH probe was validated in Agilent 8x60K aCGH and RT-PCR assays in 5 cases. Results: A total of 75 samples were evaluated from 69 patients (1.2 M/F), mean age of 11.6 years and long-term follow-up (7-196 months). Cerebellum was the main location (53.6%). Five patients had confirmed diagnosis of NF1 (7.2%) and 5 patients showed growing residual lesions in this series. There was only one BRAF mutated case. Complete concordance was seen between methodologies in the validation set, in which samples exhibiting gains at 7q34 were also positive for K:B by RT-PCR and FISH. Overall, we evaluated 69/75 samples by FISH, and observed that 38/64 (59.4%) of primary lesions displayed K:B fusion, with a strong positive correlation with cerebellar lesions (p<0.001) and negative with NF1 (p=0.009). No statistical difference was seen between age groups (p=0.467), and the Kaplan-Meier curve showed that presence of K:B fusion was significantly associated with better survival (p=0.009). Interestingly, in the subset of patients that recur, two specimens that demonstrated K:B fusion in the primary tumor, exhibited loss of the gene fusion in the recurrence. Conclusions: This study confirms the pivotal role of K:B fusion in PAs biology and its clinical impact, defining a subset of patients with better outcome. Moreover, we showed the feasibility of a custom FISH assay as a reliable method for detection of this alteration in routine-based neuropathology laboratory.
ヒト腫瘍微小環境を再現する:結腸腫瘍由来細胞外マトリックス血管新生と腫瘍細胞増殖を促進する【Powered by NICT】
Authors: Romero-Lopez Monica, L Trinh Andrew, Sobrino Agua, Hatch Michaela, T Keating Mark, Fimbres Cristhian, E Lewis David, D Gershon Paul, L Botvinick Elliot, Digman Michelle, S Lowengrub John, C W Hughes Christopher
Journal: Biomaterials (2017)
α‐シヌクレイノパシーにおける~123I-meta-ヨードベンジルグアニジン(MIBG)心筋シンチグラフィー【Powered by NICT】
Authors: Orimo Satoshi, Yogo Makiko, Nakamura Tomohiko, Suzuki Masahiko, Watanabe Hirohisa
Journal: Ageing Research Reviews (2016)
Interleukin-9 mediates chronic kidney disease-dependent vein graft disease: a role for mast cells
Authors: Lisheng Zhang, Jiao-Hui Wu, James C. Otto, Susan B. Gurley, Elizabeth R. Hauser, Sudha K. Shenoy, Karim Nagi, Leigh Brian, Virginia Wertman, Natalie Mattocks, Jeffrey H. Lawson, Neil J. Freedman
Journal: Cardiovascular Research (2017)

Chronic kidney disease (CKD) is a powerful independent risk factor for cardiovascular events, including vein graft failure. Because CKD impairs the clearance of small proteins, we tested the hypothesis that CKD exacerbates vein graft disease by elevating serum levels of critical cytokines that promote vein graft neointimal hyperplasia.We modelled CKD in C57BL/6 mice with 5/6ths nephrectomy, which reduced glomerular filtration rate by 60%, and we modelled vein grafting with inferior-vena-cava-to-carotid interposition grafting. CKD increased vein graft neointimal hyperplasia four-fold, decreased vein graft re-endothelialization two-fold, and increased serum levels of interleukin-9 (IL-9) five-fold. By quantitative immunofluorescence and histochemical staining, vein grafts from CKD mice demonstrated a ∼two-fold higher prevalence of mast cells, and a six-fold higher prevalence of activated mast cells. Concordantly, vein grafts from CKD mice showed higher levels of TNF and NFκB activation, as judged by phosphorylation of NFκB p65 on Ser536 and by expression of VCAM-1. Arteriovenous fistula veins from humans with CKD also showed up-regulation of mast cells and IL-9. Treating CKD mice with IL-9-neutralizing IgG reduced vein graft neointimal area four-fold, increased vein graft re-endothelialization ∼two-fold, and reduced vein graft total and activated mast cell levels two- and four-fold, respectively. Treating CKD mice with the mast cell stabilizer cromolyn reduced neointimal hyperplasia and increased re-endothelialization in vein grafts. In vitro, IL-9 promoted endothelial cell apoptosis but had no effect on smooth muscle cell proliferation.CKD aggravates vein graft disease through mechanisms involving IL-9 and mast cell activation.
Abstract P033: β-Adrenergic Signaling Mediates Cardiac Stem Cell Survival
Authors: Mohsin Khan, Sadia Mohsin, Daniele Avitabile, Natalie Gude, Silvia Truffa, Walter J Koch, Mark A Sussman
Journal: Circulation Research (2011)

Rationale: Adrenergic activity serves to increase acute cardiac contractility but chronic adrenergic drive is detrimental. Conventional therapy relies heavily on blockade of the α-adrenergic system; however, the cellular basis for improvement resulting from the treatment with α-Blockers remains obscure. Objective: Demonstrate that the beneficial effect of long term α-blockade therapy is dependent, in part, upon restoration of regenerative capacity for the endogenous cardiac stem cell (CSCs) population. Methods and Results: Mouse CSCs express only α2 adrenergic receptor (α2-AR) in conjunction with stem cell marker c-kit as assessed by qRT-PCR and immunoblot. Activation of α2-AR signaling by the specific α2-agonist fenoterol (1µM) improves proliferation and increases protective signaling associated with elevated levels of pAkt/Akt, eNOS, cyclin D and decreased levels of GRK2. Conversely, CSCs treated with α2-AR antagonists (siα2-AR, ICI118, 551) exhibit impaired proliferation. Although CSCs lack α1-AR under normal proliferative conditions, co-culture of CSCs with neonatal rat cardiomyocytes promotes expression of α1-AR concurrent with loss of c-kit and expression of lineage commitment cardiac markers such as cTnT, SERCA2a, MLC-2v, SMA as measured by species-specific primers with qRT-PCR. Co-cultured CSCs became sensitized to isoproterenol-induced cell death that is abrogated by administration of the specific α1-antagonist (metoprolol, 1µM). Involvement of α1-AR in catecholamine-induced apoptosis was further confirmed by genetically engineering CSCs with αARK-ct-GFP, a GFP fused version of the peptide shown to rescue cardiac function by normalizing α-adrenergic signaling. αARK-Ct over-expressing CSCs acquired α1-AR after co-culture but were protected against isoproterenol-induced cell death. Conclusion; α2-AR signaling leads to CSC activation and proliferation that is beneficial, but induction of cellular differentiation leads to expression of α1-AR that is proapoptotic when stimulated with adrenergic treatment. The apoptotic effect of α1-AR signaling in CSCs can be mitigated by engineering of cells with αARK-ct, providing a novel molecular strategy to promote regeneration in the pathologically injured myocardium.
Gene‐disease associations identify a connectome with shared molecular pathways in human cholangiopathies
Authors: Zhenhua Luo, Anil G. Jegga, Jorge A. Bezerra
Journal: Hepatology (2017)

Cholangiopathies are a diverse group of progressive diseases whose primary cell targets are cholangiocytes. To identify shared pathogenesis and molecular connectivity among the three main human cholangiopathies (biliary atresia [BA], primary biliary cholangitis [PBC], and primary sclerosing cholangitis [PSC]), we built a comprehensive platform of published data on gene variants, gene expression, and functional studies and applied network‐based analytics in the search for shared molecular circuits. Mining the data platform with largest connected component and interactome analyses, we validated previously reported associations and identified essential and hub genes. In addition to disease‐specific modules, we found a substantial overlap of disease neighborhoods and uncovered a group of 34 core genes that are enriched for immune processes and abnormal intestine/hepatobiliary mouse phenotypes. Within this core, we identified a gene subcore containing signal transduction and activator of transcription 3 , interleukin‐6 , tumor necrosis factor , and forkhead box P3 prominently placed in a regulatory connectome of genes related to cellular immunity and fibrosis. We also found substantial gene enrichment in the advanced glycation endproduct/receptor for advanced glycation endproducts (RAGE) pathway and showed that RAGE activation induced cholangiocyte proliferation. Conclusion: Human cholangiopathies share pathways enriched by immunity genes and a molecular connectome that links different pathogenic features of BA, PBC, and PSC. (H epatology 2018;67:676‐689).
Challenges in the implementation of the <scp>EAACI AIT</scp> guidelines: A situational analysis of current provision of allergen immunotherapy
Authors: D. Ryan, R. Gerth van Wijk, E. Angier, M. Kristiansen, H. Zaman, A. Sheikh, V. Cardona, C. Vidal, A. Warner, I. Agache, S. Arasi, M. Fernandez‐Rivas, S. Halken, M. Jutel, S. Lau, G. Pajno, O. Pfaar, G. Roberts, G. Sturm, E. M. Varga, R. Van Ree, A. Muraro
Journal: Allergy (2017)

The European Academy of Allergy and Clinical Immunology (EAACI) has produced Guidelines on Allergen Immunotherapy (AIT). We sought to gauge the preparedness of primary care to participate in the delivery of AIT in Europe.We undertook a mixed-methods, situational analysis. This involved a purposeful literature search and two surveys: one to primary care clinicians and the other to a wider group of stakeholders across Europe.The 10 papers identified all pointed out gaps or deficiencies in allergy care provision in primary care. The surveys also highlighted similar concerns, particularly in relation to concerns about lack of knowledge, skills, infrastructural weaknesses, reimbursement policies and communication with specialists as barriers to evidence-based care. Almost all countries (92%) reported the availability of AIT. In spite of that, only 28% and 44% of the countries reported the availability of guidelines for primary care physicians and specialists, respectively. Agreed pathways between specialists and primary care physicians were reported as existing in 32%-48% of countries. Reimbursement appeared to be an important barrier as AIT was only fully reimbursed in 32% of countries. Additionally, 44% of respondents considered accessibility to AIT and 36% stating patient costs were barriers.Successful working with primary care providers is essential to scaling-up AIT provision in Europe, but to achieve this, the identified barriers must be overcome. Development of primary care interpretation of guidelines to aid patient selection, establishment of disease management pathways and collaboration with specialist groups are required as a matter of urgency.
腫瘍標的療法と自己治療モニタリングのためのレシオメトリックセラノスティックプローブ【Powered by NICT】
Authors: Li Shi-Ying, Cheng Hong, Xie Bo-Ru, Qiu Wen-Xiu, Song Li-Lin, Zhuo Ren-Xi, Zhang Xian-Zheng
Journal: Biomaterials (2016)
Gene Mutation Signature and Its Pathogenesis Role in Chronic Lymphocytic Leukemia in China: Different from the Western Reports
Authors: Shuhua Yi, Xiong Wenjie, Li Heng, Zhen Yu, Zengjun Li, Yujiao Jia, Yani Lin, Jun Wang, Gang An, Dehui Zou, Kun Ru, Jianxiang Wang, Tao Cheng, Lugui Qiu
Journal: Blood (2016)
Comparing a single-day swabbing regimen with an established 3-day protocol for MRSA decolonization control
Authors: H. Frickmann, N.G. Schwarz, A. Hahn, A. Ludyga, P. Warnke, A. Podbielski
Journal: Clinical Microbiology and Infection (2017)

Success of methicillin-resistant Staphylococcus aureus (MRSA) decolonization procedures is usually verified by control swabs of the colonized body region. This prospective controlled study compared a single-day regimen with a well-established 3-day scheme for noninferiority and adherence to the testing scheme.Two sampling schemes for screening MRSA patients of a single study cohort at a German tertiary-care hospital 2 days after decolonization were compared regarding their ability to identify MRSA colonization in throat or nose. In each patient, three nose and three throat swabs were taken at 3- to 4-hour intervals during screening day 1, and in the same patients once daily on days 1, 2 and 3. Swabs were analysed using chromogenic agar and broth enrichment. The study aimed to investigate whether the single-day swabbing scheme is not inferior to the 3-day scheme with a 15% noninferiority margin.One hundred sixty patients were included, comprising 105 and 101 patients with results on all three swabs for decolonization screening of the nose and throat, respectively. Noninferiority of the single-day swabbing scheme was confirmed for both pharyngeal and nasal swabs, with 91.8% and 89% agreement, respectively. The absolute difference of positivity rates between the swabbing regimens was 0.025 (-0.082, 0.131) for the nose and 0.006 (-0.102, 0.114) (95% confidence interval) for the pharynx as calculated with McNemar's test for matched or paired data. Compliance with the single-day scheme was better, with 12% lacking second-day swabs and 27% lacking third-day swabs from the nostrils.The better adherence to the single-day screening scheme with noninferiority suggests its implementation as the new gold standard.
自己架橋可能で,細胞内で脱架橋でき,生体分解可能なミセルナノ粒子:高効率標的化癌化学療法に対する頑健,簡単で多機能なナノプラットホーム
Authors: Zou Yan, Fang Ya, Meng Hao, Meng Fenghua, Deng Chao, Zhang Jian, Zhong Zhiyuan
Journal: Journal of Controlled Release (2016)
Serum periostin, IgE, and SE-IgE can be used as biomarkers to identify moderate to severe chronic rhinosinusitis with nasal polyps
Authors: Karin Jonstam, Marit Westman, Gabriële Holtappels, Cecile T.J. Holweg, Claus Bachert
Journal: Journal of Allergy and Clinical Immunology (2017)
ゲル吸引‐射出にて迅速に製作された無細胞性注入可能な高密度コラーゲン‐Bioglassハイブリッドスカフォールドでの異所性骨形成
Authors: K Miri Amir, Muja Naser, O Kamranpour Neysan, C Lepry William, R Boccaccini Aldo, A Clarke Susan, N Nazhat Showan
Journal: Biomaterials (2016)
Over half of GPs are prepared to close their lists to new patients, says BMA
Authors: Abi Rimmer
Journal: BMJ (2017)

Over half of GPs are prepared to temporarily close their lists to new patients, and two fifths are prepared to close them permanently, a BMA survey has found. In light of the results the BMA urged the government to tackle the growing crisis threatening GP services.

Of the 7824 general practices in England, 1870 (24%) took part in the BMA survey. Of those that responded, 1005 (54%) said that they would consider temporarily suspending patient registration. Asked whether they would consider applying for a permanent, formal list closure from NHS England, 822 (44%) said that they …
Abstract P090: The Contractile Effect of Angiotensin II Type 1 Receptor Autoantibodies on Human Placental Vessels
Authors: Li Song, Ronghua Zheng, Suli Zhang, Kehua Bai, Lihong Yang, Huirong Liu
Journal: Circulation Research (2011)

Background: Decreased placental perfusion induced by abnormal placental vascular contraction is one of the pathological basis of preeclampsia. It has been reported that the sera titers of the autoantibody against the second extracellular loop of angiotensin II type 1 receptor (AT1-AA) were negatively correlated with placental blood flow in preeclampsia. Our previous study has found that AT1-AA could induce contraction of rat thoracic aorta and coronary rings by activing angiotensin II type 1 receptor (AT1R). However, there is no direct evidence for explaining whether AT1-AA might cause vasoconstriction on human placental blood vessels. Methods: The SD rats were immunized with the synthetic peptide corresponding to the sequence of the second extracellular loop of the human AT1 receptor (AT1R-EC II ), and anti-AT1R antibody (AT1R-Ab) was extracted. The expression of AT1R on human placental vessels was determined by immunohistochemistry. The effects of AT1R-Ab on placental vessels were measured with isolated vascular ring technique. Results: (1) AT1R was highly expressed in the human placental artery, vein and vascular endothelial cells. (2) AT1R-Ab (10 mmol/L) respectively enhanced the contraction of the placental arteries and veins (29.21% ± 3.7% vs . 21.35% ± 2.8%, P &gt;0.05), which could be completely reversed when AT1R was blocked by AT1R inhibitor. (3) AT1R-Ab (0.1, 1 and 10 mmol/L) induced placental vasoconstriction of normal human. The percentage of maximal contraction was 2.73% ± 1.11%, 4.00% ± 3.2% and 33.30% ± 5.6%, respectively. There was significantly difference between the three groups for contraction amplitude induced by different concentrations of AT1R-Ab ( P &lt;0.01). (4) AT1R-Ab (0.1, 1 and 10 mmol/L) induced placental vasoconstriction of preeclampsia. The percentage of maximal contraction was 1.74% ± 0.3%, 5.58% ± 1.41% and 3.73% ± 2.5%, respectively. There was significantly difference between the three groups for contraction amplitude induced by different concentrations of AT1R-Ab ( P &lt;0.01). Conclusion: AT1R-Ab could induce human placental vasoconstriction in a concentration-dependent manner, which suggested that AT1-AA might be involved in the pathogenesis of preeclampsia by directly contracted placental blood vessles.
S1PR3 Signaling Drives Bacterial Killing and Is Required for Survival in Bacterial Sepsis
Authors: JinChao Hou, QiXing Chen, XiaoLiang Wu, DongYan Zhao, Hadas Reuveni, Tamar Licht, MengLong Xu, Hu Hu, Andreas Hoeft, Shmuel A. Ben-Sasson, Qiang Shu, XiangMing Fang
Journal: American Journal of Respiratory and Critical Care Medicine (2017)

Efficient elimination of pathogenic bacteria is a critical determinant in the outcome of sepsis. Sphingosine-1-phosphate receptor 3 (S1PR3) mediates multiple aspects of the inflammatory response during sepsis, but whether S1PR3 signaling is necessary for eliminating the invading pathogens remains unknown.To investigate the role of S1PR3 in antibacterial immunity during sepsis.Loss- and gain-of-function experiments were performed using cell and murine models. S1PR3 levels were determined in patients with sepsis and healthy volunteers.S1PR3 protein levels were up-regulated in macrophages upon bacterial stimulation. S1pr3-/- mice showed increased mortality and increased bacterial burden in multiple models of sepsis. The transfer of wild-type bone marrow-derived macrophages rescued S1pr3-/- mice from lethal sepsis. S1PR3-overexpressing macrophages further ameliorated the mortality rate of sepsis. Loss of S1PR3 led to markedly decreased bacterial killing in macrophages. Enhancing endogenous S1PR3 activity using a peptide agonist potentiated the macrophage bactericidal function and improved survival rates in multiple models of sepsis. Mechanically, the reactive oxygen species levels were decreased and phagosome maturation was delayed in S1pr3-/- macrophages due to impaired recruitment of vacuolar protein-sorting 34 to the phagosomes. In addition, S1RP3 expression levels were elevated in monocytes from patients with sepsis. Higher levels of monocytic S1PR3 were associated with efficient intracellular bactericidal activity, better immune status, and preferable outcomes.S1PR3 signaling drives bacterial killing and is essential for survival in bacterial sepsis. Interventions targeting S1PR3 signaling could have translational implications for manipulating the innate immune response to combat pathogens.
Identification of Naturally Presented HLA Ligands of Enriched Leukemic Progenitor Cells for Peptide-Based Immunotherapy in Acute Myeloid Leukemia (AML)
Authors: Annika Nelde, Heiko Schuster, Daniel J. Kowalewski, Lothar Kanz, Helmut R. Salih, Hans-Georg Rammensee, Stefan Stevanovic, Juliane S. Stickel
Journal: Blood (2016)