tbuckley/cabot-search huggingface dataset:
Egg allergen specific IgE diversity predicts resolution of egg allergy in the population cohort HealthNuts
Authors: Thanh D. Dang, Rachel L. Peters, Jennifer J. Koplin, Shyamali C. Dharmage, Lyle C. Gurrin, Anne‐Louise Ponsonby, David J. Martino, Melanie Neeland, Mimi L. K. Tang, Katrina J. Allen
Journal: Allergy (2018)

IgE-mediated egg allergy presents as one of the most common food allergies in children. Measurement of egg white specific IgE (sIgE) levels in serum or skin prick test has been shown to be a poor predictor of clinical allergy to raw egg white, and also to baked or cooked egg. Recent developments in component resolved diagnostic (CRD) technology have enabled us to improve the way in which we diagnose and predict peanut allergy by examining IgE specificity to individual peptides.We aimed to investigate whether egg CRD could improve current methods to diagnose various egg allergy phenotypes as well as predict the development of tolerance to egg.Using the HealthNuts cohort of food challenge-proven egg allergic and egg-sensitized and egg-tolerant, age-matched 12-month infants with longitudinal follow-up at 2 and 4 years (n = 451), we measured serum egg white, Gal d 1, 2, 3 and 5 sIgE using ImmunoCAP.Gal d 1 sensitization increased the risk of persistent egg allergy by 2.5-fold. The production of sIgE to all four egg allergens (Gal d 1, 2, 3 or 5) increased the risk of having persistent raw egg allergy fourfold (OR 4.19 (95% CI: 1.25-14.07). We did not find any improvements of using Gal d 1, 2, 3 or 5 to diagnose current egg allergy compared to egg white sIgE.Sensitization to multiple egg allergens Gal d 1, 2, 3 or 5 may be a prognostic marker that could be useful for patient management and identifying individuals at risk of developing persistent egg allergy.
Local Retention Versus Systemic Release of Soluble VEGF Receptor-1 Are Mediated by Heparin-Binding and Regulated by Heparanase
Authors: ShaySela, ShiraNatanson-Yaron, EyalZcharia, IsraelVlodavsky, SimchaYagel, EliKeshet
Journal: Circulation Research (2011)

Rationale:The vascular endothelial growth factor (VEGF) decoy receptor soluble VEGF-R1 (sVEGF-R1) is thought to protect the cells that produce it from adverse VEGF signaling. To accomplish this role, a mechanism for pericellular retention of sVEGF-R1 is required. Local retention may also prevent the accumulation of high circulating levels of sVEGF-R1 and resulting interference with homeostatic VEGF functions in remote organs. Objective:To reveal natural storage depots of sVEGF-R1 and determine mechanisms underlying its pericellular retention. To uncover natural mechanisms regulating its systemic release. Methods and Results:We show that both the canonical and human-specific isoforms of sVEGF-R1 are strongly bound to heparin. sVEGF-R1 produced by vascular smooth muscle cells is stored in the vessel wall and can be displaced from isolated mouse aorta by heparin. Another major reservoir of sVEGF-R1 is the placenta. Heparin increases the level of sVEGF-R1 released by cultured human placental villi, and pregna...
Characterisation of the nasal microbiota in granulomatosis with polyangiitis
Authors: Rennie L Rhee, Antoine G Sreih, Catherine E Najem, Peter C Grayson, Chunyu Zhao, Kyle Bittinger, Ronald G Collman, Peter A Merkel
Journal: Annals of the Rheumatic Diseases (2018)

Prior studies have suggested a potential link between nasal microbes and granulomatosis with polyangiitis (GPA; Wegener's), but these studies relied on culture-dependent methods. This study comprehensively examined the entire community of nasal microbiota (bacteria and fungi) in participants with GPA compared with healthy controls using deep sequencing methods.16S rRNA and internal transcribed spacer gene sequencing were performed on nasal microbial DNA isolated from nasal swabs of 60 participants with GPA and 41 healthy controls. Alpha and beta diversity were assessed as well as the relative abundance of the most abundant bacterial and fungal taxa. The effects of covariates including disease activity and immunosuppressive therapies on microbial composition were evaluated.Compared with controls, participants with GPA had a significantly different microbial composition (weighted UniFrac p=0.04) and lower relative abundance of Propionibacterium acnes and Staphylococcus epidermidis (for both, false discovery rate-corrected p=0.02). Disease activity in GPA was associated with a lower abundance of fungal order Malasseziales compared with participants with GPA in remission (p=0.04) and controls (p=0.01). Use of non-glucocorticoid immunosuppressive therapy was associated with 'healthy' nasal microbiota while participants with GPA who were off immunosuppressive therapy had more dysbiosis (weighted UniFrac p=0.01). No difference in the relative abundance of Staphylococcus aureus was observed between GPA and controls.GPA is associated with an altered nasal microbial composition, at both the bacterial and fungal levels. Use of immunosuppressive therapies and disease remission are associated with healthy microbial communities.
Abstract 151: The Cardioprotective Effect of HIF-1α/miR-21/PDCD4 Pathway During Transplanted Heart Cold Storage
Authors: Liang Zhu, Jingzhou Mu, Chang Qu, Yunhong Wu, Shuzhuang Li, Tonghui Ma
Journal: Circulation Research (2017)

Hypoxia-inducible factor 1 (HIF-1) is a transcription factor that plays a major role under hypoxia condition. Cold storage during heart transplantation causes the donor heart long-term hypoxia. There are some evidence indicating a conceivable HIF-1α/miR-21/PDCD4 pathway. We assessed the hypothesis that Hypoxia-inducible factor -1α (HIF-1α) has a cardioprotective effect during donor heart cold storage, by making the miR-21 upregulate reduce the expression of PDCD4. We establish the rats heart cold storage model and stratified into 6-hour groups from 0 to 24 hours. Western blot and RT-qPCR were performed to detected the expression of HIF-1α, miR-21, PDCD4 and PTEN. After cold storage the expression of HIF-1α increased from 0 to 6 hours, then gradually decreased but the expression level was relatively higher compared to control group. The miR-21 was upregulated from 0 to 12 hous then downregulated. The mRNA expression of PDCD4 was upregulated gradually, but the protein expression was significantly downregulated in the 12 hour then continued to upregulate. Interestingly, the expression level of miR-21 was highest in the 12 hour, which indicated miR-21 could inhibite the PDCD4. And we subsequently detected the mRNA of PTEN which can inhibit the HIF-1α and be inhibited by miR-21.The expression of PTEN was also significantly downregulated in the 12 hour. In conclusion, there is possible interaction between HIF-1α and miR-21, and the conceivable HIF-1α/miR-21/PDCD4 pathway play a protective role in cold storage of heart. Key words: Heart Transplantation, Cold storage, miR-21, HIF-1α, PDCD4
Phospholipase A2 in Vascular Disease
Authors: EvaHurt-Camejo, GermánCamejo, HelenaPeilot, KatarinaÖörni, PetriKovanen
Journal: Circulation Research (2001)

Secretory phospholipase A2 (PLA2) can be proatherogenic both in the circulation and in the arterial wall. In blood plasma, PLA2 can modify the circulating lipoproteins and so induce formation of small dense LDL particles, which are associated with increased risk for cardiovascular disease. In the arterial wall, PLA2 can hydrolyze lipoproteins. The PLA2-modified lipoproteins bind tightly to extracellular proteoglycans, which may lead to their enhanced retention in the arterial wall. The modified lipoproteins may also aggregate and fuse, which can lead to accumulation of their lipids within the extracellular matrix. The PLA2-modified particles are more susceptible to further modifications by other enzymes and agents and can be taken up by macrophages, leading to accumulation of intracellular lipids. In addition, lysophospholipids and free fatty acids, the hydrolysis products of PLA2, promote atherogenesis. Thus, these lipid mediators can be carried, either by the PLA2-modified lipoproteins themselves or by ...
Autonomic Nervous System and Benign Essential Hypertension in Man
Authors: Jean-Louiscuche, Ottokuchel, Andrébarbeau, Yveslanglois, Rogerboucher, Jacquesgenest
Journal: Circulation Research (1974)

The effect of upright posture as a physiological stimulus of the adrenergic nervous system was studied in 56 subjects with benign essential hypertension. The subjects received a controlled-sodium diet. Blood pressure, heart rate, catecholamines, plasma renin activity, and urinary creatinine, sodium, and potassium excretion were measured in the recumbent and upright positions. We found an alteration in the blood pressure response in subjects with benign essential hypertension; the postural increase in the mean blood pressure in normotensive subjects (3.18 ± 1.35 mm Hg) progressively disappeared and was replaced by a postural decrease in subjects with more severe stable hypertension (-6.71 ± 2.42 mm Hg). The hypertensive subjects also lacked the usual increase in urinary excretion of norepinephrine. A significant increase in plasma renin activity associated with a significant decrease in plasma norepinephrine occurred in subjects with labile hypertension with postural tachycardia. Finally, we found a highly...
Upregulation of MG53 Induces Diabetic Cardiomyopathy Through Transcriptional Activation of Peroxisome Proliferation-Activated Receptor α
Authors: FenghuaLiu, RuishengSong, YuanqingFeng, JiaojiaoGuo, YanminChen, YongZhang, TaoChen, YanruWang, YanyiHuang, Chuan-YunLi, ChunmeiCao, YanZhang, XinliHu, Rui-pingXiao
Journal: Circulation (2015)

Background—Diabetic cardiomyopathy, which contributes to >50% diabetic death, is featured by myocardial lipid accumulation, hypertrophy, fibrosis, and cardiac dysfunction. The mechanism underlying diabetic cardiomyopathy is poorly understood. Recent studies have shown that a striated muscle-specific E3 ligase Mitsugumin 53 (MG53, or TRIM72) constitutes a primary causal factor of systemic insulin resistance and metabolic disorders. Although it is most abundantly expressed in myocardium, the biological and pathological roles of MG53 in triggering cardiac metabolic disorders remain elusive. Methods and Results—Here we show that cardiac-specific transgenic expression of MG53 induces diabetic cardiomyopathy in mice. Specifically, MG53 transgenic mouse develops severe diabetic cardiomyopathy at 20 weeks of age, as manifested by insulin resistance, compromised glucose uptake, increased lipid accumulation, myocardial hypertrophy, fibrosis, and cardiac dysfunction. Overexpression of MG53 leads to insulin resistant...
PTU-072 Current trends in endoscopic procedure numbers in south and east birmingham from four hospital centres 2010–2015
Authors: P Harvey, K Ward, G Hodges, M Andrew, S Cooper, M Iacucci, T Iqbal, S Ghosh, N Sharma, B Walt, S Wyatt, H Brown, N Bhala
Journal: Gut (2017)

Introduction  A Cancer Research UK report1 suggests GI endoscopy demand will increase dramatically, with a 45% increase over 5 years. We compare regional data to national projections, to provide reliable regional estimates to guide capacity planning.  Method  JAG mandates the routine data submission from all hospital/Trust sites. This included adult OGD and colonoscopy procedure counts at University Hospital Birmingham and Heart of England NHS Trusts, comprising 4 hospital centres.  Results  Above predicted increases in OGD procedures were observed, with 27.8% growth over 5 years. (22% increase over two years was higher than predicted over five).  Colonoscopy growth was consistent with national projections at 32.6% growth in 5 years (10% increase over 2 years, consistent with national estimates). Bowel cancer screening lists occur at both Trusts.  Flexible sigmoidoscopy growth varied between Trusts (17.1% since 2013 at UHB, 3.3% reduction at HEFT). Bowel scope, although established at UHB is not yet at HEFT, was fundamental to projections.  Conclusion  These data demonstrate large recent growth in endoscopy conducted in South/East Birmingham for OGD and colonoscopy, with greater than predicted growth in the former. Given current challenges of limited endoscopy rooms and staff retention, urgent capacity planning is required in this area and likely across the Midlands.  Reference  . Brown H, Wyatt S, Croft S, Gale N, Turner A, Mulla A. Scoping the Future, An evaluation of endoscopy capacity across the NHS in England. Cancer Research UK, Sept 2015  Disclosure of Interest  None Declared
Japanese cedar pollinosis in Tokyo residents born after massive national afforestation policy
Authors: Mitsuyoshi Urashima, Daiya Asaka, Tomonori Endo, Sachiko Omae, Naoki Sugimoto, Shinya Takaishi, Ryoto Mitsuyoshi, Tsuguhisa Nakayama, Hitoshi Nagakura, Tomohiko Endo, Taisuke Akutsu, Hiroshi Tachimoto, Hiromi Kojima
Journal: Allergy (2018)

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Combined 68Ga-NOTA-PRGD2 and 18F-FDG PET/CT Can Discriminate Uncommon Meningioma Mimicking High-Grade Glioma
Authors: Deling Li, Jingjing Zhang, Nan Ji, Xiaobin Zhao, Kun Zheng, Zhen Qiao, Fang Li, Lixin Lang, Andrei Iagaru, Gang Niu, Zhaohui Zhu, Xiaoyuan Chen
Journal: Clinical Nuclear Medicine (2018)

Objectives Uncommon pathological subtypes of meningioma may present with severe peritumoral brain edema and mimic high-grade glioma (HGG). In a prospective cohort study of 68 Ga-NOTA-PRGD2 PET/CT to evaluate glioma, we occasionally observed that a combination of 68 Ga-NOTA-PRGD2 and 18 F-FDG was able to differentiate these 2 lesion types. Methods From 2013 to 2016, 21 patients suspected of HGG by MRI were recruited for evaluation using 68 Ga-NOTA-PRGD2 PET/CT. Brain 18 F-FDG PET/CT was performed within 3 days for comparison, and the tumor was surgically removed. The PET results were compared with integrin αvβ3 expression and microvascular density quantification of tumor samples. Results Of the 21 recruited patients, 5 patients were finally pathologically diagnosed as uncommon meningioma with severe peritumoral brain edema, including chordoid meningioma (n = 1), angiomatous meningioma (n = 1), and mixed angiomatous and microcystic meningioma (n = 3). Sixteen were diagnosed as HGG. All the meningioma lesions (n = 5) exhibited intense and homogeneous 68 Ga-NOTA-PRGD2 uptake with higher SUVmax on 68 Ga-NOTA-PRGD2 PET (1.64–7.86; mean ± SD, 4.23 ± 2.48) than the HGG lesions (0.81–2.99; mean ± SD, 1.57 ± 0.33; P = 0.0047). Moreover, the uptake ratios of 68 Ga-NOTA-PRGD2 over 18 F-FDG, normalized as lg100 * SUVmax (RGD / FDG), in the uncommon meningiomas were significantly higher than those in HGG (1.87 ± 1.36 vs 1.04 ± 0.87, P = 0.0001). A cutoff value of 1.58 was able to discriminate between these lesion types. There were positive correlations among the expression level of integrin αvβ3, microvascular density, and the tumor-to-background ratio derived from 68 Ga-NOTA-PRGD2 PET ( P &lt; 0.05). Conclusions This study reveals a specific imaging pattern of uncommon meningioma mimicking HGG, in which 68 Ga-NOTA-PRGD2 PET provided added value to 18 F-FDG PET.
Abstract 2126: Therapeutic Evaluation of Corticosteroid Therapy for Ventricular Tachycardia Associated with Cardiac Sarcoidosis -Application of High Resolution Electrocardiography-
Authors: Kenji Yodogawa, Yoshihiko Seino, Norihiko Ono, Chikao Ibuki, Toshihiko Ohara, Yoshinori Kobayashi, Takao Katoh, Kyoichi Mizuno
Journal: Circulation (2008)

Background The outcome of cardiac sarcoidosis (CS) is sometimes fatal. Ventricular tachycardia (VT) is one of the common causes of sudden death in CS patients. In patients with definite diagnosis of CS, corticosteroid therapy should be the absolute indication. However, little is known about the effectiveness for VT. Further, there is no established method for therapeutic evaluation in CS. Thus, we investigated whether or not VT is suppressed following corticosteroid therapy and the utility of Signal Averaged Electrocardiography (SAECG) for therapeutic assessment in CS patients with VT. Methods Fifteen histological proved CS patients presenting with sustained or non-sustained VT were investigated. All of these patients were treated with predonisolone 30mg to 10mg/day, and assessed before and after corticosteroid therapy. All patients underwent SAECG in which the filtered QRS duration (f-QRS), the root mean square voltage of the terminal 40 ms (RMS 40 ) in the filtered QRS complex and the duration of low-amplitude signals &lt; 40μV (LAS 40 ) in the terminal filtered QRS complex were measured. The presence of VT was assessed by Holter monitoring. Results VT was suppressed in 6 patients {VT (−) group} and the remaining 9 patients were not {VT (+) group}. Accumulation of gallium-67 was detected more frequently in VT (−) group than in VT (+) group (66.7% vs. 11.1%, p&lt;0.05). Left ventricular ejection fraction (LVEF) was significantly higher in VT (−) group than that of VT (−) group (54.1+/−20.1 vs 32.8+/−11.7 p&lt;0.05). In VT (−) group, f-QRS and LAS 40 were significantly decreased and RMS 40 was significantly increased compared with those before corticosteroid therapy (f-QRS: 136.3+/−30.6msec vs 116.8+/−25.4msec, p&lt;0.05 LAS 40 : 68.2+/−24.0msec vs 47.8+/−22.9msec, p&lt;0.05 RMS 40 : 7.2+/−3.3 msec vs 13.3+/−7.6msec, p&lt;0.05). However, SAECG parameters did not change significantly in VT (+) group. Conclusions In the early and viable stage of the disease, corticosteroid therapy was effective for VT in CS. Reversible conduction abnormality detected by SAECG might reflect reversible arrhythmogenic substrate for the occurrence of VT. SAECG is useful for therapeutic evaluation of CS patients with VT.
Not All Complicated Appendicitis Is the Same
Authors: Diana Lee Farmer
Journal: JAMA Surgery (2018)

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Mitochondrial Stasis Reveals p62-Mediated Ubiquitination in Parkin-Independent Mitophagy and Mitigates Nonalcoholic Fatty Liver Disease
Authors: Tatsuya Yamada, Daisuke Murata, Yoshihiro Adachi, Kie Itoh, Shoichiro Kameoka, Atsushi Igarashi, Takashi Kato, Yoichi Araki, Richard L. Huganir, Ted M. Dawson, Toru Yanagawa, Koji Okamoto, Miho Iijima, Hiromi Sesaki
Journal: Cell Metabolism (2018)
Abstract 441: Role of Nitric Oxide and S-nitrosylation in Cardiomyogenesis by iPSCs
Authors: Alessandro Salerno, Konstantinos Hatzistergos, Raul Dulce, Amarylis Wanschel, Wayne Balkan, Joshua Hare
Journal: Circulation Research (2017)

Introduction: The mechanism by which signaling pathways, such as Wnt and BMP interact and modulate each other’s function is crucial to our understanding of cardiomyogenesis and cardiomyocyte proliferation. Nitric oxide (NO) is a signaling molecule that can trigger cardiac differentiation of stem cells, suggesting a cardiogenic function of NO synthase(s) (NOS). Hypothesis: NO modulates transcription factor function during pluripotency and differentiation toward a cardiac phenotype. Methods: Induced pluripotent stem cells (iPSCs) were derived from fibroblasts from wildtype mice and mice lacking S-nitrosoglutathione reductase (GSNOR -/- ), a denitrosylase that regulates protein S-nitrosylation. iPSCs were differentiated into functional cardiomyocytes from embryoid bodies (EBs) via the hanging-drop method. Results: During differentiation into cardiomyocytes, GSNOR -/- iPSC-derived cardiomyocytes exhibited reduced expression of mesoderm induction-related ( Brachyury ), cardiac mesoderm (Kdr , Isl-1 ) and cardiac progenitor genes ( Nkx2.5 , GATA4 ). Axin-1, an inducer of apoptosis and negative regulator of the Wnt signaling pathway and MAPK pathways, specifically p38, were increased on EB-Day (D)4. In contrast, SMAD1/5/8, members of the BMP canonical signaling pathway, were reduced beginning on EB-D8. Increased p38 is associated with reduced GATA4 expression and differentiation of human ES cells into cardiomyocytes. Decreased SMAD1/5/8 is likely at least in part responsible for the reduced expression of Nkx2.5. Conclusions: Our findings support that the absence of GSNOR modulates Wnt/β-catenin and BMP signaling pathways during cardiogenesis, resulting in reduced expression of mesoderm, cardiac mesoderm and cardiac progenitor genes. These findings are expected to have important implications for regenerative medicine and can provide new targets for iPS cell-based therapy.