tbuckley/cabot-search huggingface dataset:
The Vascular Targeting Property of Paclitaxel Is Enhanced by SU6668, a Receptor Tyrosine Kinase Inhibitor, Causing Apoptosis of Endothelial Cells and Inhibition of Angiogenesis
Authors: Elitza Naumova, Paolo Ubezio, Angela Garofalo, Patrizia Borsotti, Linda Cassis, Elena Riccardi, Eugenio Scanziani, Suzanne A. Eccles, Maria R. Bani, Raffaella Giavazzi
Journal: Clinical Cancer Research (2006)

Abstract Purpose: Different antiangiogenic approaches have been proposed in cancer treatment where therapeutic efficacy has been shown with the addition of cytotoxic agents. Here, we used SU6668, a small-molecule receptor tyrosine kinase inhibitor, to investigate the combinatorial effect with paclitaxel on the cellular populations of the developing vasculature. Experimental Design: The effect of this combination was evaluated in vitro in a 72-hour proliferation assay on human umbilical vein endothelial cells (HUVEC) and human microvascular endothelial cells derived from lungs, endothelial cells, aortic smooth muscle cells, and human ovarian carcinoma cells sensitive (1A9) and resistant (1A9-PTX22) to paclitaxel. Combination data were assessed by isobologram analysis. Cell survival was determined by terminal deoxyribonucleotide transferase–mediated nick-end labeling and Annexin V staining. The activity of the combination in vivo was evaluated in fibroblast growth factor-2–induced angiogenesis in Matrigel plugs s.c. implanted in mice. The 1A9-PTX22, paclitaxel-resistant xenograft model was used to evaluate tumor response. Results: Combination index values and isobologram analysis showed synergy in inhibition of proliferation of HUVEC, human microvascular endothelial cells derived from lungs, and aortic smooth muscle cells. The combination induced greater apoptosis in HUVEC than the single agents. The addition of paclitaxel to the treatment with SU6668 significantly decreased the hemoglobin content and the number of CD31-positive vessels in Matrigel plugs in vivo. The combination of the drugs was more active than either single agent against 1A9-PTX22 xenografts; the tumor growth delay was accompanied by a significant reduction of vascular density. Conclusions: These findings show that the activity of angiogenesis inhibitors on vascular cells could be potentiated when administered in combination with chemotherapeutic agents that themselves have vascular targeting properties.
Fall incidence and fall risk factors in people with rheumatoid arthritis
Authors: E Smulders, C Schreven, V Weerdesteyn, F H J van den Hoogen, R Laan, W Van Lankveld
Journal: Annals of the Rheumatic Diseases (2009)

Falls in people with rheumatoid arthritis (RA) are an underestimated problem. Almost all patients with RA develop lower extremity problems, which may increase their risk of falling because of impaired levels of physical activity, mobility and postural stability as well as diminished strength and proprioception.1 2 Only three studies have reported fall frequency in patients with RA. The annual proportion of fallers in patients with RA (mean age 59.2) ranges from 33% to 35%.1 2 3 The fall incidence rate of 0.62 falls/person-year1 is well above the fall incidence rate reported in healthy elderly people (0.45).4 5 However, all three studies used retrospective self-reports to measure fall …
Purification and characterization of fetal hematopoietic cells that express the common acute lymphoblastic leukemia antigen (CALLA).
Authors: P Hokland, P Rosenthal, J D Griffin, L M Nadler, J Daley, M Hokland, S F Schlossman, J Ritz
Journal: The Journal of Experimental Medicine (1983)

Fetal hematopoietic cells that express the common acute lymphoblastic leukemia antigen (CALLA) were purified from both fetal liver and fetal bone marrow by immune rosetting with sheep erythrocytes coated with rabbit anti-mouse immunoglobulin and by fluorescence-activated cell sorting. Dual fluorescence techniques disclosed that these cells were heterogenous with respect to the expression of a series of differentiation and activation antigens defined by monoclonal antibodies. Thus, whereas all CALLA+ cells were Ia+ and expressed two activation antigens, J2 and T10, only 30-50% expressed B1 antigen. Furthermore, using methanol-fixed cells, it could be shown that approximately 20% contained intracytoplasmic mu chains (cyto-mu) and that approximately 15% were positive for the terminal transferase enzyme (TdT) marker. The CALLA+ fetal cells thus closely resemble the childhood acute lymphoblastic leukemia cell with respect to surface marker phenotype. A population of CALLA- cells devoid of mature erythroid and myeloid surface markers was found to contain higher numbers of TdT+ cells but lower numbers of cyto-mu, B1, and Ia+ cells than the CALLA+ subset. In vitro analysis of normal, purified CALLA+ cells demonstrated that incubation at 37 degrees C with J5 monoclonal antibody specific for CALLA resulted in the specific modulation of surface antigen. Similar results have previously been obtained with CALLA+ tumor cells. Although phenotypic analysis of CALLA+ cells suggests that these cells are relatively immature lymphoid cells, CALLA+ cells do not appear to contain either myeloid precursor cells (CFU-G/M) or the earliest lymphoid stem cells.
Functional and Structural Adaptations of Coronary Microvessels Distal to a Chronic Coronary Artery Stenosis
Authors: Oana Sorop, Daphne Merkus, Vincent J. de Beer, Birgit Houweling, Adrian Pistea, Edward O. McFalls, Frans Boomsma, Heleen M. van Beusekom, Wim J. van der Giessen, Ed VanBavel, Dirk J. Duncker
Journal: Circulation Research (2008)

Distal to a chronic coronary artery stenosis, structural remodeling of the microvasculature occurs. The microvascular functional changes distal to the stenosis have not been studied in detail. We tested the hypothesis that microvascular structural remodeling is accompanied by altered regulation of coronary vasomotor tone with increased responsiveness to endothelin-1. Vasomotor tone was studied in coronary microvessels from healthy control swine and from swine 3 to 4 months after implantation of an occluder that causes a progressive coronary narrowing, resulting in regional left ventricular dysfunction and blunted myocardial vasodilator reserve. Arterioles (≈200-μm passive inner diameter at 60 mm Hg) were isolated from regions perfused by the stenotic left anterior descending and normal left circumflex coronary arteries and studied in vitro. Passive pressure–diameter curves demonstrated reduced distensibility of subendocardial left anterior descending compared with subendocardial left circumflex or control arterioles, suggestive of structural remodeling. Myogenic responses were blunted in subendocardial left anterior descending compared with left circumflex arterioles, reflecting altered smooth muscle function. However, vasodilator responses to nitroprusside and bradykinin were not different in the endocardium, suggesting preserved endothelium and smooth muscle responsiveness. Finally, vasoconstrictor responses to endothelin-1 were enhanced in left anterior descending arterioles compared with left circumflex or control arterioles. Regional myocardial vascular conductance responses to bradykinin and endothelin in vivo confirmed the in vitro observations. In conclusion, inward remodeling of coronary microvessels distal to a stenosis is accompanied by exaggerated vasoconstrictor responses to endothelin-1. These structural and functional alterations may aggravate flow abnormalities distal to a chronic coronary artery stenosis.
FIVE-YEAR FOLLOW-UP OF POLYTETRAFLUOROETHYLENE-COVERED STENTS COMPARED WITH BARE METAL STENTS IN AORTOCORONARY SAPHENOUS VEIN GRAFTS: THE RANDOMIZED BARRICADE TRIAL
Authors: Philippe Genereux, Sheldon Goldberg, Charles O'Shaughnessy, Mark Midei, Robert M. Siegel, Gary S. Mintz, Ecaterina Cristea, George Dangas, Alexandra J. Lansky, Roxana Mehran, Gregg W. Stone
Journal: Journal of the American College of Cardiology (2011)
Steroid Sulfatase and Estrogen Sulfotransferase in Colon Carcinoma: Regulators of Intratumoral Estrogen Concentrations and Potent Prognostic Factors
Authors: Ryuichiro Sato, Takashi Suzuki, Yu Katayose, Koh Miura, Kenichi Shiiba, Hiroo Tateno, Yasuhiro Miki, Junichi Akahira, Yukiko Kamogawa, Shuji Nagasaki, Kuniharu Yamamoto, Takayuki Ii, Shinichi Egawa, Dean B. Evans, Michiaki Unno, Hironobu Sasano
Journal: Cancer Research (2009)

Previous epidemiologic and in vitro studies have indicated a potential involvement of estrogens in the pathogenesis of human colon carcinoma, but the precise roles of estrogens have remained largely unknown. Therefore, in this study, we first measured intratumoral concentrations of estrogens in 53 colon carcinomas using liquid chromatography-electrospray ionization tandem mass spectrometry (LC-ESI-MS). Tissue concentrations of total estrogen [estrone (E(1)) + estradiol] and E(1) were significantly (2.0- and 2.4-fold, respectively) higher in colon carcinoma tissues than in nonneoplastic colonic mucosa (n = 31), and higher intratumoral concentrations of total estrogen and E(1) were significantly associated with adverse clinical outcome. Intratumoral concentration of total estrogen was significantly associated with the combined status of steroid sulfatase (STS) and estrogen sulfotransferase (EST), but not with that of aromatase. Thus, we subsequently examined the STS/EST status in 328 colon carcinomas using immunohistochemistry. Immunoreactivities for STS and EST were detected in 61% and 44% of the cases, respectively. The -/+ group of the STS/EST status was inversely associated with Dukes' stage, depth of invasion, lymph node metastasis, and distant metastasis and positively correlated with Ki-67 labeling index of the carcinomas. In addition, this -/+ group had significantly longer survival, and a multivariate analysis revealed the STS/EST status as an independent prognostic factor. Results from our present study showed that the STS/EST status of carcinoma tissue determined intratumoral estrogen levels and could be a significant prognostic factor in colon carcinoma, suggesting that estrogens are locally produced mainly through the sulfatase pathway and play important roles in the progression of the disease.
Idiopathic hypertrophic subaortic stenosis viewed by wide-angle, phased-array echocardiography.
Authors: R P Martin, H Rakowski, J French, R L Popp
Journal: Circulation (1979)

A wide-angle, phased array ultrasonic sector scanner was used to view the heart in 18 patients with idiopathic hypertrophic subaortic stenosis (IHSS).The rapid systolic anterior motion (SAM) of the mitral apparatus appeared quite separate from movement of either the left ventricular posterior wall or prominent papillary muscles.The SAM always occurred in a location judged to be the chordal end of the mitral leaflets.The SAM involved the whole mitral apparatus more extensively in patients with high outflow tract gradients at rest (> 60 mm Hg), and in all patients during Valsalva maneuver or amyl nitrite inhalation.The mitral apparatus, including the papillary muscles, was anteriorly displaced in short-axis images of these patients' hearts.True end-systolic cavity obliteration was not seen at rest in any patient, since a small space persisted posteriorly between the papillary muscles in short-axis images.We believe these data support some and negate other previously proposed mechanisms for the mitral valve SAM and abnormal left ventricular dynamic geometry in patients with IHSS.Localized subaortic thick septal myocardium was seen in each case.Additionally, we noted an unusual echo pattern within the myocardium and especially in portions of the thick septum.This pattern was present along 20-100% (mean 50%) of the septal length, and 16-40% (mean 25%) of the left ventricular circumference, and in the posterobasal myocardium in two patients.We speculate that this echo pattern within the thick septal myocardium may be related to abnormal myocardial structure or myocardial fibrosis noted previously by histologic methods.IN THE 20 YEARS since the original anatomic' and functional2 description of idiopathic hypertrophic sub- aortic stenosis (IHSS), few diseases have sparked so much interest and controversy.314 Since the late 1960s, single-dimensional echocardiography has been proposed and used as a sensitive, convenient, noninvasive tool for the diagnosis and therapeutic assessment
Musculoskeletal Symptoms in Patients With Cryopyrin‐Associated Periodic Syndromes: A Large Database Study
Authors: Laetitia Houx, Eric Hachulla, Isabelle Kone‐Paut, Pierre Quartier, Isabelle Touitou, Xavier Guennoc, Gilles Grateau, Mohamed Hamidou, Bénédicte Neven, Jean‐Marie Berthelot, Thierry Lequerré, Pascal Pillet, Irène Lemelle, Michel Fischbach, Agnès Duquesne, Pierre Le Blay, Claire Le Jeunne, Jérome Stirnemann, Christine Bonnet, Dominique Gaillard, Lilian Alix, Renaud Touraine, François Garcier, Christophe Bedane, Anne‐Laure Jurquet, Pierre Duffau, Amar Smail, Camille Frances, Martine Grall‐Lerosey, Pascal Cathebras, Tu Anh Tran, Sandrine Morell‐Dubois, Anne Pagnier, Christophe Richez, Laurence Cuisset, Valérie Devauchelle‐Pensec
Journal: Arthritis & Rheumatology (2015)

To determine the type and frequency of musculoskeletal symptoms at onset and during followup of cryopyrin-associated periodic syndromes (CAPS).We retrospectively recorded the articular and muscular symptoms of patients with CAPS followed up in French hospitals. Data were presented as frequencies or the median (range), and patient groups were compared using chi-square test, Fisher's exact test, and Mann-Whitney test.The study included 133 patients (33 children), 20 with familial cold autoinflammatory syndrome, 88 with Muckle-Wells syndrome, 22 with chronic infantile neurologic, cutaneous, articular syndrome, and 3 with unclassified CAPS. The median age was 35 years (range 0-78 years) at the time of the study, 1 year (range 0-41 years) at symptom onset, and 23 years (range 0-58 years) at diagnosis. The disease was sporadic in 17% of the patients. Cutaneous symptoms predominated at onset (77%), followed by articular symptoms (30%). The p.Thr348Met and p.Arg260Trp NLRP3 mutations were significantly associated with the presence and absence of articular symptoms at onset, respectively. During followup, 86% of the patients had musculoskeletal symptoms, 88% had arthralgia, and 58% had arthritis, but only 9% had joint destruction. Tendinopathies occurred in 21.5% of the patients, tender points in 16.5%, and myalgia in 33%. Only 3 patients had typical knee deformities. Radiographs were rarely obtained. Except for bone deformities, osteoarticular symptoms occurred at similar frequencies in the different CAPS phenotypes.Joint manifestations were frequent in all CAPS phenotypes. Bone deformities were rare. Musculoskeletal manifestations varied within given families but tended to worsen over time.
GINA 2015: the latest iteration of a magnificent journey
Authors: Jean Bousquet, Marc Humbert
Journal: European Respiratory Journal (2015)

The Global Initiative for Asthma (GINA) represents a remarkable source document that has changed the course of asthma in most countries. The first asthma guidelines have been published in Australasia, UK [1] and the USA [2]. Canadian and French recommendations proposed the concept of control [3, 4], and the National Asthma Education and Prevention Program Expert Panel Report initiated the concept of risk for asthma [5]. However, GINA is globally considered to be the prominent asthma recommendation building on existing knowledge and providing several updates or revisions since it was introduced in 1995 [2, 6, 7]. GINA 2015 represents a significant advance over the previous iteration, with a more practical approach and an increased appreciation of asthma as a public health problem [8]. Due to the expected impact of GINA 2015 it is mandatory to assess strengths and weaknesses although many of these cannot be ruled out due to the lack of information currently available. In the September issue of the ERJ, a new report summarises key updates to the GINA global strategy document <http://ow.ly/PKjhw>
The Effect of 19-Norandrostenolone on Experimentally-Induced Atheroma in Cockerels
Authors: R. S. F. CAMPBELL, T. D. V. LAWRIE, J. C. MACLAURIN, R. PIRRIE
Journal: Circulation Research (1960)

The anabolic and weakly androgenie compound 19-norandrostenolone has been administered to cholesterol-fed cockerels in 2 dose levels. A marked fall in serum cholesterol occurred with the lower dose level and a significant reduction in the incidence of coronary artery lesion was noted with the higher dose level.
FoxM1 regulates re-annealing of endothelial adherens junctions through transcriptional control of β-catenin expression
Authors: Muhammad K. Mirza, Ying Sun, Yidan D. Zhao, Hari-Hara S.K. Potula, Randall S. Frey, Steven M. Vogel, Asrar B. Malik, You-Yang Zhao
Journal: The Journal of Experimental Medicine (2010)

Repair of the injured vascular intima requires a series of coordinated events that mediate both endothelial regeneration and reannealing of adherens junctions (AJs) to form a restrictive endothelial barrier. The forkhead transcription factor FoxM1 is essential for endothelial proliferation after vascular injury. However, little is known about mechanisms by which FoxM1 regulates endothelial barrier reannealing. Here, using a mouse model with endothelial cell (EC)-restricted disruption of FoxM1 (FoxM1 CKO) and primary cultures of ECs with small interfering RNA (siRNA)-mediated knockdown of FoxM1, we demonstrate a novel requisite role of FoxM1 in mediating endothelial AJ barrier repair through the transcriptional control of β-catenin. In the FoxM1 CKO lung vasculature, we observed persistent microvessel leakage characterized by impaired reannealing of endothelial AJs after endothelial injury. We also showed that FoxM1 directly regulated β-catenin transcription and that reexpression of β-catenin rescued the defective AJ barrier–reannealing phenotype of FoxM1-deficient ECs. Knockdown of β-catenin mimicked the phenotype of defective barrier recovery seen in FoxM1-deficient ECs. These data demonstrate that FoxM1 is required for reannealing of endothelial AJs in order to form a restrictive endothelial barrier through transcriptional control of β-catenin expression. Therefore, means of activating FoxM1-mediated endothelial repair represent a new therapeutic strategy for the treatment of inflammatory vascular diseases associated with persistent vascular barrier leakiness such as acute lung injury.
Hematopoietic AMPK β1 reduces mouse adipose tissue macrophage inflammation and insulin resistance in obesity
Authors: Sandra Galic, Morgan D. Fullerton, Jonathan D. Schertzer, Sarah Sikkema, Katarina Marcinko, Carl R. Walkley, David Izon, Jane Honeyman, Zhi-Ping Chen, Bryce J. van Denderen, Bruce E. Kemp, Gregory R. Steinberg
Journal: Journal of Clinical Investigation (2011)

Individuals who are obese are frequently insulin resistant, putting them at increased risk of developing type 2 diabetes and its associated adverse health conditions. The accumulation in adipose tissue of macrophages in an inflammatory state is a hallmark of obesity-induced insulin resistance. Here, we reveal a role for AMPK β1 in protecting macrophages from inflammation under high lipid exposure. Genetic deletion of the AMPK β1 subunit in mice (referred to herein as β1(-/-) mice) reduced macrophage AMPK activity, acetyl-CoA carboxylase phosphorylation, and mitochondrial content, resulting in reduced rates of fatty acid oxidation. β1(-/-) macrophages displayed increased levels of diacylglycerol and markers of inflammation, effects that were reproduced in WT macrophages by inhibiting fatty acid oxidation and, conversely, prevented by pharmacological activation of AMPK β1-containing complexes. The effect of AMPK β1 loss in macrophages was tested in vivo by transplantation of bone marrow from WT or β1(-/-) mice into WT recipients. When challenged with a high-fat diet, mice that received β1(-/-) bone marrow displayed enhanced adipose tissue macrophage inflammation and liver insulin resistance compared with animals that received WT bone marrow. Thus, activation of AMPK β1 and increasing fatty acid oxidation in macrophages may represent a new therapeutic approach for the treatment of insulin resistance.
Lymphocytic gastritis and Helicobacter pylori infection in gastric lymphoma.
Authors: A Miettinen, T J Karttunen, M Alavaikko
Journal: Gut (1995)

Lymphocytic gastritis and primary gastric lymphoma are rare conditions with unknown aetiology. It has recently been suggested that Helicobacter pylori has a role in the pathogenesis of both of them. The occurrence of lymphocytic gastritis and H pylori was studied in a series of patients with primary gastric lymphoma. The cases of primary gastric lymphomas (n = 35) diagnosed in years 1970-1993 were identified. The specimens of 22 cases contained gastric mucosa sufficiently so that the number of intra-epithelial lymphocytes, severity of gastritis, and occurrence of H pylori could be studied. Lymphocytic gastritis was detected in seven of 22 patients (32%), and in most cases both in antral and body mucosa. Atrophy of the body glands was significantly more severe in lymphocytic gastritis patients. H pylori was detected in 13 of all 22 patients (59%); two of seven lymphocytic gastritis patients (29%), and 11 of 15 (73%) of patients without lymphocytic gastritis were H pylori positive. Patients with gastric lymphoma have significantly increased prevalence of lymphocytic gastritis. Rarity of H pylori in these patients might be connected with atrophic changes in body mucosa. Further studies are needed to show the significance of lymphocytic gastritis as a precursor of gastric lymphoma.
Identification of an imprinting control region affecting the expression of all transcripts in the Gnas cluster
Authors: Christine M Williamson, Martin D Turner, Simon T Ball, Wade T Nottingham, Peter Glenister, Martin Fray, Zuzanna Tymowska-Lalanne, Antonius Plagge, Nicola Powles-Glover, Gavin Kelsey, Mark Maconochie, Jo Peters
Journal: Nature Genetics (2006)
Integrated molecular analysis of clear-cell renal cell carcinoma
Authors: Yusuke Sato, Tetsuichi Yoshizato, Yuichi Shiraishi, Shigekatsu Maekawa, Yusuke Okuno, Takumi Kamura, Teppei Shimamura, Aiko Sato-Otsubo, Genta Nagae, Hiromichi Suzuki, Yasunobu Nagata, Kenichi Yoshida, Ayana Kon, Yutaka Suzuki, Kenichi Chiba, Hiroko Tanaka, Atsushi Niida, Akihiro Fujimoto, Tatsuhiko Tsunoda, Teppei Morikawa, Daichi Maeda, Haruki Kume, Sumio Sugano, Masashi Fukayama, Hiroyuki Aburatani, Masashi Sanada, Satoru Miyano, Yukio Homma, Seishi Ogawa
Journal: Nature Genetics (2013)