tbuckley/cabot-search huggingface dataset:
BMP-driven NRF2 activation in esophageal basal cell differentiation and eosinophilic esophagitis
Authors: Ming Jiang, Wei-Yao Ku, Zhongren Zhou, Evan S. Dellon, Gary W. Falk, Hiroshi Nakagawa, Mei-Lun Wang, Kuancan Liu, Jun Wang, David A. Katzka, Jeffrey H. Peters, Xiaopeng Lan, Jianwen Que
Journal: Journal of Clinical Investigation (2015)

Tissue homeostasis requires balanced self-renewal and differentiation of stem/progenitor cells, especially in tissues that are constantly replenished like the esophagus. Disruption of this balance is associated with pathological conditions, including eosinophilic esophagitis (EoE), in which basal progenitor cells become hyperplastic upon proinflammatory stimulation. However, how basal cells respond to the inflammatory environment at the molecular level remains undetermined. We previously reported that the bone morphogenetic protein (BMP) signaling pathway is critical for epithelial morphogenesis in the embryonic esophagus. Here, we address how this pathway regulates tissue homeostasis and EoE development in the adult esophagus. BMP signaling was specifically activated in differentiated squamous epithelium, but not in basal progenitor cells, which express the BMP antagonist follistatin. Previous reports indicate that increased BMP activity promotes Barrett's intestinal differentiation; however, in mice, basal progenitor cell-specific expression of constitutively active BMP promoted squamous differentiation. Moreover, BMP activation increased intracellular ROS levels, initiating an NRF2-mediated oxidative response during basal progenitor cell differentiation. In both a mouse EoE model and human biopsies, reduced squamous differentiation was associated with high levels of follistatin and disrupted BMP/NRF2 pathways. We therefore propose a model in which normal squamous differentiation of basal progenitor cells is mediated by BMP-driven NRF2 activation and basal cell hyperplasia is promoted by disruption of BMP signaling in EoE.
Abstract 229: Omega-3 fatty acids strongly induce apoptosis in human breast cancer cells in vitro and in vivo via formation of reactive oxygen species and caspase 8 activation
Authors: Pan Wang, Ki-Sung Kang, Noriko Yamabe, Masayuki Fukui, Taylor Jay, B T. Zhu
Journal: Cancer Research (2010)

Abstract [Hypothesis] The present study sought to investigate the in vitro and in vivo anticancer effect of two representative omega-3 fatty acids, docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA), with a focus on assessing the role of fatty acid-induced oxidative stress and apoptosis as mechanisms for their anticancer actions. [Methods] We used in vitro cell culture of MCF-7 human breast cancer cells and in vivo athymic nude mice model to study the effect of omega-3 fatty acids on cancer cell proliferation and the mechanism of the cell death. [Results] In vitro studies showed that DHA and EPA each strongly reduced the viability and DNA synthesis of MCF-7 human breast cancer cells in culture, and they also promoted cell death via apoptosis. Mechanistically, accumulation of reactive oxygen species and activation of caspase 8 contributed critically to the induction of apoptotic cell death. Co-presence of antioxidants or a selective inhibition or knockdown of caspase 8 each effectively abrogated the cytotoxic effect of DHA. Using athymic nude mice as an in vivo model, we found that feeding animals with 5% fish oil-containing diet for 6 weeks significantly reduced the growth of MCF-7 human breast cancer cells through inhibition of cancer cell proliferation as well as promotion of cell death. Using 3-nitrotyrosine as a parameter, we confirmed that fish oil diet significantly increased oxidative stress in tumor cells in vivo. Analysis of fatty acid content in plasma and tissues showed that feeding animals a 5% fish oil diet significantly increased DHA and EPA levels in both normal and tumorous mammary tissues by 329 and 300%, respectively. [Conclusion] The results of this investigation clearly showed that omega-3 fatty acids strongly inhibited human breast cancer proliferation both in vitro and in vivo via formation of reactive oxygen species and induction of apoptosis by caspase 8 activation. This study calls for further studies in human subjects to assess the effectiveness of fish oil as a dietary supplement in the treatment of certain types of cancers. Note: This abstract was not presented at the AACR 101st Annual Meeting 2010 because the presenter was unable to attend. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 229.
THE METHOD OF FEEDING IN CASES OF INTUBATION OF THE LARYNX BY POSITION, HEAD DOWNWARD, ON AN INCLINED PLANE.
Authors: W. E. CASSELBERRY
Journal: JAMA (1889)

Since the presentation to the Chicago Medical Society, in September last, of the preliminary verbal report on this method of feeding as just then devised by me, the subject has assumed such importance, and the method, as modified through further experience, has been so successfully practiced within a limited circle, that it is desirable to widely promulgate the device in its perfected and modified aspects. The unavoidable entrance of food material into ready hypnotized several times go to sleep with confidence and without emotion or agitation. Suggestion may act upon the vaso-motor circulation; a red spot may be produced upon the body by suggestion, or even a blister may be raised, and hæmorrhages and bloody stigmata may be induced. Bernheim suggests that experiments might be instituted to determine to what degree imagination may influence certain functions in the waking condition. We know that micturition and defecation are greatly influenced by
Epigenetic Control of Gene Expression in the Lung
Authors: Ivana V. Yang, David A. Schwartz
Journal: American Journal of Respiratory and Critical Care Medicine (2011)

Section:ChooseTop of pageAbstract <<EPIGENETIC MECHANISMSROLE OF THE ENVIRONMENT I...EPIGENTICS MARKS AND THE ...EPIGENETICS AND LUNG DISE...EPIGENOMIC PROFILINGCHALLENGES IN UNDERSTANDI...ReferencesCITING ARTICLES
Long term performance of small-diameter vascular grafts made of a poly(ether)urethane–polydimethylsiloxane semi-interpenetrating polymeric network
Authors: Giorgio Soldani, Paola Losi, Massimo Bernabei, Silvia Burchielli, Dante Chiappino, Silvia Kull, Enrica Briganti, Dario Spiller
Journal: Biomaterials (2009)
Effect of Methyldopa in Carcinoid Disease
Authors: G. I. Nicholson, M. C. Evans, R. O. H. Irvine
Journal: BMJ (1962)

and increased in size in Case 7 despite further courses of methotrexate. SummaryThe rationale of methotrexate therapy is discussed and a short review of the literature given.From January 1, 1960, to June 30, 1961, seven cases of chorionepithelioma were treated with methotrexate in the Gynaecological Department, University of Hong Kong.Summaries of the seven case records are given.While hysterectomy, which was performed in all the seven cases, is thought to be necessary in the treatment of chorionepithelioma, the increase in size and number of pulmonary metastases in five of the seven cases seems to suggest that manipulation causes further spread of the disease.In the absence of profuse vaginal bleeding, therefore, methotrexate should be given before surgical extirpation of the uterus if a reasonably certain diagnosis is made.The optimal dose for a Chinese woman of average weight seems to be 100 mg. per course (5 mg.four times a day for five days).The dosage cannot, however, be calculated on the basis of body weight alone.The scheme used is described.The interval between courses is found to be two weeks in most instances.The number of courses should not be fixed, and methotrexate should be given until the male frog test becomes persistently negative, pulmonary opacities completely disappear, and secondaries elsewhere in the body completely resolve.While stomatitis is the commonest toxic manifestation of any significance, diarrhoea, generalized erythematous skin rash, and alopecia are also encountered.Two patients (Cases 3 and 7) are dead, after having been treated with methotrexate for 6 and 10 months respectively.Two patients (Cases 1 and 5) have been lost trace of three months and one month respectively after the commencement of methotrexate therapy.Both of them were showing marked improvement when they were last seen.Three patients (Cases 2, 4, and 6) remain well with no sign of disease whatsoever 27, 22, and 12 months respectively after their first admissions.
THE EFFECT OF ICD REPLACEMENT ON THE REQUIREMENT FOR SURGICAL RE-INTERVENTION DUE TO INFECTIOUS AND NON-INFECTIOUS CAUSES.
Authors: Joep Thijssen, C. Jan Willem Borleffs, Mihály K. de Bie, Johannes B. van Rees, Guido H. van Welsenes, Ernst E. van der Wall, Lieselot van Erven, Jeroen J. Bax, Suzanne C. Cannegieter, Martin J. Schalij
Journal: Journal of the American College of Cardiology (2010)
<i>CCR</i> 20th Anniversary Commentary: In Search of Cetuximab's First Indication—Combination Therapy with Irinotecan in Colorectal Cancer
Authors: Daniel J. Hicklin
Journal: Clinical Cancer Research (2015)

Abstract The research article by Prewett and colleagues, published in the May 1, 2002, issue of Clinical Cancer Research, provided important translational data that extended earlier preclinical and clinical studies with the human–murine chimeric anti-EGFR monoclonal antibody C225. Subsequent clinical trials with C225 led to the demonstration of its efficacy in combination with irinotecan and regulatory approval for the treatment of metastatic colorectal cancer. Clin Cancer Res; 21(7); 1505–7. ©2015 AACR. See related article by Prewett et al., Clin Cancer Res 2002;8(5) May 2002;994–1003
β-Adrenergic Receptor–Mediated Cardiac Contractility Is Inhibited via Vasopressin Type 1A-Receptor–Dependent Signaling
Authors: Douglas G. Tilley, Weizhong Zhu, Valerie D. Myers, Larry A. Barr, Erhe Gao, Xue Li, Jianliang Song, Rhonda L. Carter, Catherine A. Makarewich, Daohai Yu, Constantine D. Troupes, Laurel A. Grisanti, Ryan C. Coleman, Walter J. Koch, Steven R. Houser, Joseph Y. Cheung, Arthur M. Feldman
Journal: Circulation (2014)

Enhanced arginine vasopressin levels are associated with increased mortality during end-stage human heart failure, and cardiac arginine vasopressin type 1A receptor (V1AR) expression becomes increased. Additionally, mice with cardiac-restricted V1AR overexpression develop cardiomyopathy and decreased β-adrenergic receptor (βAR) responsiveness. This led us to hypothesize that V1AR signaling regulates βAR responsiveness and in doing so contributes to development of heart failure.Transaortic constriction resulted in decreased cardiac function and βAR density and increased cardiac V1AR expression, effects reversed by a V1AR-selective antagonist. Molecularly, V1AR stimulation led to decreased βAR ligand affinity, as well as βAR-induced Ca(2+) mobilization and cAMP generation in isolated adult cardiomyocytes, effects recapitulated via ex vivo Langendorff analysis. V1AR-mediated regulation of βAR responsiveness was demonstrated to occur in a previously unrecognized Gq protein-independent/G protein receptor kinase-dependent manner.This newly discovered relationship between cardiac V1AR and βAR may be informative for the treatment of patients with acute decompensated heart failure and elevated arginine vasopressin.
PRISON EPIDEMIC OF FLEXNER'S DYSENTERY
Authors: L. L. STANLEY
Journal: JAMA (1930)

On Saturday morning, Aug. 3, 1929, fifteen of the 4,246 inmates of the California State Prison at San Quentin appeared at the early sick call with a history of having been attacked during the previous night with severe cramps in the abdomen followed by profuse diarrhea, aching of the bones and prostration. At the noon sick call the number of patients had increased to seventy-nine, all suffering from the same complaint. The incidence of the disease is given in table 1. From the beginning of the outbreak until August 18, when this epidemic had practically ceased, there were 946 inmates who had been affected by this dysentery. Cultures of the stools were made, and<i>Bacillus dysenteriae</i>Flexner was isolated. In the prison there are four places where the inmates eat: the hospital, the female ward, the officers' and guards' dining room, where all the free people eat, and the general
Abstract 9934: Levels of Plasma Pentraxin 3 Predict Presence of Thin-cap Fibroatheroma in Patients with Stable Angina Pectoris: Assessment by Optical Coherence Tomography
Authors: Seiji Koga, Satoshi Ikeda, Tomoo Nakata, Takeo Yoshida, Masayoshi Takeno, Yuji Koide, Koji Maemura
Journal: Circulation (2011)

Background: Thin-cap fibroatheroma (TCFA) is the primary type of rupture prone plaque, but biomarkers predicting it are not established. Recently, pentraxin 3 (PTX3) has been shown to be a novel biomarker specific to vascular inflammation. The aim of this study was to clarify the association between plasma PTX3 level and TCFA as determined by optical coherence tomography (OCT) in patients with stable angina pectoris (SAP). Methods: Thirty-four patients with SAP who underwent OCT at de novo culprit lesions before percutaneous coronary intervention were evaluated. TCFA was defined as a plaque with lipid contents in &gt;90°and with thinnest part of the fibrous cap measuring &lt;70μ m. Plasma PTX3 and serum high sensitive C-reactive protein (hsCRP) were measured among these patients. Plasma PTX3 level was categorized into low (&lt; 25th percentile), intermediate (25th to 75th percentiles), and high (&gt; 75th percentile) groups. Results: Fourteen patients with TCFA and 20 patients without TCFA were identified. Levels of PTX3 (median [interquartile range]) were significantly greater in patients with TCFA than without TCFA (4.66 [2.44 - 6.80]) vs. 2.60 [1.79 - 3.18] ng/mL; p = 0.009). Levels of hsCRP were comparable between the two groups. PTX3 level significantly inversely correlated with fibrous cap thickness (r = -0.53, p = 0.009), but hsCRP did not. The frequency of TCFA was 22, 29, and 88% in low, intermediate, and high PTX3 group, respectively (p = 0.009). Univariate analysis revealed that hypercholesterolemia, statin use, and level of PTX3 were related to the presence of TCFA. Multivariate logistic regression analysis in these factors showed that plasma PTX3 level was the significant independent factor associated with TCFA existence (OR, 1.99; 95%CI, 1.10 - 3.58; p = 0.023). The area under the receiver-operating characteristics curve for PTX3 level for prediction of TCFA was 0.766 (p = 0.009). The optimal cut-off value of PTX3 for predicting TCFA was 2.88 ng/mL (sensitivity 71%, specificity 70%). Conclusions: Plasma PTX3 level was associated with the presence of TCFA and thinner fibrous cap thickness at coronary culprit lesions in patients with SAP. These findings suggest that plasma PTX3 might be a useful marker reflecting the plaque vulnerability.
Molecular alterations critical to the development of arteriosclerotic plaques: a role for environmental agents.
Authors: A Penn
Journal: Environmental Health Perspectives (1989)

Cardiovascular disease (CVD) is the single greatest cause of death in the United States and in Western Europe. There is strong epidemiologic evidence for an interaction of environmental and genetic factors in the development of clinically significant episodes of CVD. However, the specific contributions of each of these components to the onset and development of CVD remain unclear. According to the monoclonal hypothesis, arteriosclerotic plaques, the principal lesions associated with CVD, are monoclonal in origin and can be considered benign smooth muscle cells tumors of the artery wall. It follows that somatic cell alterations, possibly brought about by chemical mutagens or viruses, may play critical roles in plaque formation. During the past decade, evidence has been presented from a number of laboratories, including ours, that in animal model systems, both viruses and chemical carcinogens can play a role in the appearance and development of arteriosclerotic plaques. We have recently provided evidence consistent with the view that somatic cell alterations are critical to plaque development in man: DNA from human arteriosclerotic plaques. transforms cells in vitro and injection of these transformed cells into nude mice results in tumor formation. Thus, plaque DNA behaves similarly to tumor DNA under defined assay conditions.
Sulfatides
Authors: M. Merten, S. Motamedy, S. Ramamurthy, F.C. Arnett, P. Thiagarajan
Journal: Circulation (2003)

Sulfatides are sulfated glycosphingolipids expressed on the surface of erythrocytes, leukocytes, and platelets. Sulfatides interact with several cell adhesion molecules involved in hemostasis. Beta2-glycoprotein I is an anionic phospholipid-binding plasma protein, and the phospholipid-bound form is the target for most anti-phospholipid antibodies that are associated with recurrent thrombosis, miscarriages, and neurological symptoms. In this study, we examined whether beta2-glycoprotein I forms a complex with sulfatides and thereby becomes a target for anti-phospholipid antibodies.Beta2-glycoprotein I binds to surface-bound sulfatides but not to other glycolipids, such as ceramide, cerebrosides, sphingomyelin, or ganglioside. At a sulfatide coating density of 1 microg/well, beta2-glycoprotein I reaches half-maximal binding at 2.5 microg/mL, and the binding is saturated at 10 microg/mL. The binding of beta2-glycoprotein I also depends on the coating density of sulfatides in the well. At a constant beta2-glycoprotein I concentration of 5 microg/mL, maximal binding of beta2-glycoprotein I is observed at a coating density of 1 mug/well. The serum from 14 patients with anti-cardiolipin antibodies, a subset of anti-phospholipid antibodies, bound to sulfatide-bound beta2-glycoprotein I and previous absorption on cardiolipin-coated surfaces decreased the immunoreactivity toward sulfatide-beta2-glycoprotein I complex by >50% in 12 of 14 patients. Furthermore, immunoaffinity-purified anti-cardiolipin antibodies from 4 of 5 patients reacted with sulfatide-bound beta2-glycoprotein I.These results show that not only anionic phospholipids, as commonly known, but also sulfatides are targets for most anti-phospholipid antibodies. We therefore postulate that interactions of these antibodies with sulfatides may contribute to some of the clinical symptoms of the anti-phospholipid antibody syndrome.
Regulation of ICAM‐3 and other adhesion molecule expressions on eosinophils <i>in vitro</i>. Effects of dexamethasone
Authors: M. Juan, C. Vilardell, J. Yagüe, C. Picado, J. Mullol, J. Roca‐Ferrer, M. Fuentes, M. Pérez, C. Picado, M. Juan
Journal: Allergy (1999)

Background : ICAM‐3 has been recently identified as the third leukocyte‐function associated‐1 (LFA‐1) ligand. ICAM‐3 is expressed in eosinophils, but its regulation has not been studied. The objective of this study was to investigate the differential expression of ICAM‐3 and other adhesion molecules (AM) on the surface of eosinophils. We also evaluated the effects of dexamethasone on AM expression. Methods : Normodense eosinophils were isolated from peripheral blood and incubated with calcium ionophore A23187 (calcimycin) with and without dexamethasone. Expression of AM was assessed by flow cytometry and expressed as fluorescence mean intensity (FMI). Results : Peripheral blood eosinophils constitutively expressed low levels of ICAM‐1 and ICAM‐2 (&lt;10 FMI), moderate levels (10–50 FMI) of CD29 and L‐selectin, and high levels (&gt;50 FMI) of ICAM‐3, LFA‐1, and Mac‐1. Calcium ionophore (1 μM) significantly increased Mac‐1 and ICAM‐1 expression at 6 and 24 h. L‐selectin expression decreased at 6 and 24 h, but ICAM‐2, ICAM‐3, LFA‐1, and CD29 expression did not show any significant change after calcium ionophore stimulation. Dexamethasone decreased ICAM‐3 and increased L‐selectin basal expression, and it caused a dose‐related inhibition of calcium ionophore‐induced ICAM‐1 expression. Conclusions : These findings suggest that some AM, such as ICAM‐1, Mac‐1, and L‐selectin, may be involved in adhesion during eosinophil activation and that glucocorticoids may prevent airway inflammation by regulating the expression of AM in eosinophils. The role of ICAM‐3, a leukocyte AM highly expressed in resting eosinophils, remains to be clarified.
FDA Warns Against Shared Insulin Pens
Authors: Bridget M. Kuehn
Journal: JAMA (2009)

vatchev, PhD, director of the diabetes technology program at the University of Virginia, Charlottesville. The result of 10 years of data collection and research, this system is essentially a computer simulator of the human metabolic system that is equipped with the in silico images of 300 people with type 1 diabetes: 100 children, 100 adolescents, and 100 adults, said Kovatchev. This approach, referred to as in silico modeling, is cheaper and quicker than animal testing. “We can do trials in 10 minutes that would have taken years of animal experimentation,” he said. As a case in point, in only 3 months of using the in silico modeling system, Kovatchev’s group received FDA approval to conduct a clinical trial of a fully closed-loop system using an MPC algorithm that is personalized for each individual. Similar approvals based solely on in silico testing were issued for parallel clinical trials in Italy and France. When these trials are completed, each of the 24 individuals with type 1 diabetes will have undergone two 24-hour admissions involving identical eating, sleeping, and activity patterns. The first admission is an openloop session in which glucose levels are controlled by the individuals; the second admission is under automatic closed-loop control. The results of the two admissions for each individual will be compared to determine which approach achieved better glucose control. “Closed loop looks like it can do so much better, particularly overnight,” remarked Kovatchev, referring to preliminary results from 12 individuals that were reported at the Diabetes Technology meeting in Bethesda, Md, last November. The most interesting effect was a dramatic 5-fold reduction in the number of hypoglycemic episodes observed overnight. One crucial step in development of the artificial pancreas is prevention of overnight hypoglycemia, which seems within reach with this approach, noted Kovatchev. The team’s next goal, called control to range, is to reduce the number of hypoglycemic and hyperglycemic episodes and keep patients within a target glucose range for a greater percentage of the time.
Electroshock for Atrial Flutter and Atrial Fibrillation
Authors: Jay B. Jensen
Journal: JAMA (1965)

The electrical conversion of atrial flutter and fibrillation to normal sinus rhythm is effective and safe. However, follow-up study of 50 patients showed that sinus rhythm persisted in only 42% of those patients whose arrhythmias were initially converted. The mean follow-up time was ten months. The immediate and long-term results were much better in patients with atrial flutter and in those with atrial fibrillation of less than two years' duration.