tbuckley/cabot-search huggingface dataset:
Intravesical Ad-IFNα Causes Marked Regression of Human Bladder Cancer Growing Orthotopically in Nude Mice and Overcomes Resistance to IFN-α Protein
Authors: William F. Benedict, Ziming Tao, Chang-Soo Kim, Xinqiao Zhang, Jain-Hua Zhou, Liana Adam, David J. McConkey, Angela Papageorgiou, Mark Munsell, Jennifer Philopena, Heidrun Engler, William Demers, Daniel C. Maneval, Colin P.N. Dinney, Robert J. Connor
Journal: Molecular Therapy (2004)

We have produced prolonged, high local concentrations of interferon in vivo by intravesical instillation of adenoviruses encoding interferon-alpha (Ad-IFNalpha) together with the gene transfer-enhancing agent Syn3. We found sustained interferon protein levels for days, both in normal mouse urothelium and in human bladder cancer cells growing as superficial bladder tumors in nude mice using an orthotopic bladder model developed by us. Tumor burden in the bladder was determined utilizing cancer cells containing the green fluorescent protein. Marked tumor regression was observed following two 1-h exposures of Ad-IFNalpha/Syn3 and little or no cytotoxicity was detected in normal cells. Similar intravesical instillation of clinically relevant concentrations of IFN protein alone or Ad-IFNalpha without Syn3 was ineffective. Surprisingly, in vitro, Ad-IFNalpha also caused caspase-dependent death of bladder cancer cell lines that were resistant to high concentrations of IFN-alpha protein, including the cell line used in vivo. These findings demonstrate that Ad-IFNalpha can overcome resistance to IFN-alpha protein both in vitro and in vivo and support evaluation of intravesical Ad-IFNalpha/Syn3 for the treatment of superficial bladder cancer.
Calcium Infusion for Reversal of Adverse Effects of Intravenous Verapamil
Authors: D. Lynn Morris
Journal: JAMA (1983)

VERAPAMIL hydrochloride has been shown to be useful in the treatment of symptomatic hypertrophic cardiomyopathy by decreasing left ventricular outflow obstruction, reducing left ventricular muscle mass, and increasing left ventricular diastolic compliance.<sup>1-4</sup>Verapamil-related hemodynamic and electrophysiological complications in these cases have been documented in those with high pulmonary capillary wedge pressures in the presence of left ventricular outflow obstruction, evidence of congestive heart failure, substantive atrioventricular nodal dysfunction, and hypotension.<sup>3</sup>Although clinical experience suggests that calcium may be effective in reversing the adverse effects of verapamil, such therapy has not been widely publicized.<sup>4-8</sup>We report a case of a patient with hypotension and profound bradycardia caused by verapamil therapy for hypertrophic cardiomyopathy, which responded well to calcium chloride. <h3>Report of a Case</h3> A 56-year-old woman with echocardiographic diagnosis of hypertrophic cardiomyopathy, asymmetric septal hypertrophy, and systolic anterior motion of the mitral valve was admitted to San Francisco
The Energetic State of Mitochondria Modulates Complex III Biogenesis through the ATP-Dependent Activity of Bcs1
Authors: Jelena Ostojić, Cristina Panozzo, Jean-Paul Lasserre, Cécile Nouet, Florence Courtin, Corinne Blancard, Jean-Paul di Rago, Geneviève Dujardin
Journal: Cell Metabolism (2013)
Peripheral mucoepidermoid tumour of the lung.
Authors: L. K. Green, T. L. Gallion, F. Gyorkey
Journal: Thorax (1991)

Mucoepidermoid tumours of the bronchial tree are uncommon neoplasms, which are believed to arise from terminal ducts of the proximal tracheobronchial tree. The first case of a peripheral mucoepidermoid tumour of the lung is reported.
Cilostazol Attenuates Spontaneous Microaggregation of Platelets in Type 2 Diabetic Patients With Insufficient Platelet Response to Aspirin
Authors: Shin-ichi Araki, Hiroyuki Matsuno, Masakazu Haneda, Daisuke Koya, Yosuke Kanno, Shiniji Kume, Keiji Isshiki, Hisazumi Araki, Satoshi Ugi, Hiromichi Kawai, Atsunori Kashiwagi, Takashi Uzu, Hiroshi Maegawa
Journal: Diabetes Care (2013)

Prevention of cardiovascular disease is an important therapeutic goal in patients with type 2 diabetes mellitus (1). Although a low dose of aspirin is recommended for this purpose, some patients were resistant to aspirin (2). We previously reported that spontaneous microaggregation of platelets (SMAPs) formed under no stimulation with exogenous agonists were frequently observed in type 2 diabetic patients (3,4) and a considerable number of patients receiving aspirin still showed SMAP formation (4). The aim of the current study was to investigate whether a switch from aspirin to another antiplatelet drug could improve an insufficient platelet response to aspirin in diabetic patients.

This was an open-label, single-arm, uncontrolled trial of antiplatelet treatment with 200 mg cilostazol daily (a phosphodiesterase III inhibitor) as an alternative to aspirin in 24 Japanese type 2 diabetic patients who persistently showed the inadequate SMAP formation despite treatment with …
Ligand-Directed Surface Profiling of Human Cancer Cells with Combinatorial Peptide Libraries
Authors: Mikhail G. Kolonin, Laura Bover, Jessica Sun, Amado J. Zurita, Kim-Anh Do, Johanna Lahdenranta, Marina Cardó-Vila, Ricardo J. Giordano, Diana E. Jaalouk, Michael G. Ozawa, Catherine A. Moya, Glauco R. Souza, Fernanda I. Staquicini, Akihiko Kunyiasu, Dominic A. Scudiero, Susan L. Holbeck, Edward A. Sausville, Wadih Arap, Renata Pasqualini
Journal: Cancer Research (2006)

Abstract A collection of 60 cell lines derived from human tumors (NCI-60) has been widely explored as a tool for anticancer drug discovery. Here, we profiled the cell surface of the NCI-60 by high-throughput screening of a phage-displayed random peptide library and classified the cell lines according to the binding selectivity of 26,031 recovered tripeptide motifs. By analyzing selected cell-homing peptide motifs and their NCI-60 recognition patterns, we established that some of these motifs (a) are similar to domains of human proteins known as ligands for tumor cell receptors and (b) segregate among the NCI-60 in a pattern correlating with expression profiles of the corresponding receptors. We biochemically validated some of the motifs as mimic peptides of native ligands for the epidermal growth factor receptor. Our results indicate that ligand-directed profiling of tumor cell lines can select functional peptides from combinatorial libraries based on the expression of tumor cell surface molecules, which in turn could be exploited as “druggable” receptors in specific types of cancer. (Cancer Res 2006; 66(1): 34-40)
Bowel preparation for colonoscopy: European Society of Gastrointestinal Endoscopy (ESGE) Guideline
Authors: C. Hassan, M. Bretthauer, M. Kaminski, M. Polkowski, B. Rembacken, B. Saunders, R. Benamouzig, O. Holme, S. Green, T. Kuiper, R. Marmo, M. Omar, L. Petruzziello, C. Spada, A. Zullo, J. Dumonceau
Journal: Endoscopy (2013)

<b>Background and aim: </b>This Guideline is an official statement of the European Society of Gastrointestinal Endoscopy (ESGE). It addresses the choice amongst regimens available for cleansing the colon in preparation for colonoscopy. <b>Methods:</b> This Guideline is based on a targeted literature search to evaluate the evidence supporting the use of bowel preparation for colonoscopy. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) system was adopted to define the strength of recommendation and the quality of evidence. <b>Results:</b> The main recommendations are as follows. (1) The ESGE recommends a low-fiber diet on the day preceding colonoscopy (weak recommendation, moderate quality evidence). (2) The ESGE recommends a split regimen of 4 L of polyethylene glycol (PEG) solution (or a same-day regimen in the case of afternoon colonoscopy) for routine bowel preparation. A split regimen (or same-day regimen in the case of afternoon colonoscopy) of 2 L PEG plus ascorbate or of sodium picosulphate plus magnesium citrate may be valid alternatives, in particular for elective outpatient colonoscopy (strong recommendation, high quality evidence). In patients with renal failure, PEG is the only recommended bowel preparation. The delay between the last dose of bowel preparation and colonoscopy should be minimized and no longer than 4 hours (strong recommendation, moderate quality evidence). (3) The ESGE advises against the routine use of sodium phosphate for bowel preparation because of safety concerns (strong recommendation, low quality evidence).
Time Relationship of Dynamic Events in the Cardiac Chambers, Pulmonary Artery and Aorta in Man
Authors: EUGENE BRAUNWALD, ALFRED P. FISHMAN, ANDRÉ COURNAND
Journal: Circulation Research (1956)

Exposure of the heart in the course of chest surgery affords a means of faithfully recording pressure pulses in the four chambers of the heart and in the large vessels of human subjects. This study in 13 individuals without any clinical evidence of cardiovascular disease, is concerned with the time relationship between electric and mechanical events and with the temporal sequence and respective characteristics of similar phases of the cardiac cycle in both sides of the heart. The results obtained by permutation of simultaneous pressure recordings confirm the classical observations made in dogs.
Direct costs related to rheumatoid arthritis: the patient perspective
Authors: J L Hulsemann
Journal: Annals of the Rheumatic Diseases (2005)

<b>Objective:</b> To determine rheumatoid arthritis related out of pocket expenditure (OOPE) in Germany and to disaggregate the total OOPE into contributing cost domains. <b>Methods:</b> Data for the cost analysis were drawn from a multicentre randomised controlled prospective trial to assess the effectiveness of clinical quality management in patients with rheumatoid arthritis. Both payer sources and patient cost questionnaires were used to generate health care utilisation data. All cost domains of a recently published matrix were reviewed and potential sources of OOPE were determined. Health care utilisation data were developed throughout 2001. Co-payment regulations as per January 2004 were applied in order to indicate the most recent level of OOPE in Germany. Data were analysed in both physical and monetary units using descriptive statistics. <b>Results:</b> In all, 136 patients with rheumatoid arthritis were included. Mean total OOPE per patient and year was €417.20 (SEM 38.8, median 271.2). OOPE accounted for 15.3% of the total direct costs of rheumatoid arthritis. Total OOPE were further subdivided into cost domains: "non-physician service utilisation"' (€194.40 per patient and year; SEM 24.2), "medication" (€99.00; 6.1), "transportation" (€56.20; 17.4), "visits to physicians" (€38.40; 0.6), "hospital facilities" (€24.00; 5.6), and "devices and aids" (€5.10; 0.8). <b>Conclusions:</b> Rheumatoid arthritis is associated with substantial OOPE, imposing a considerable economic burden for patients. OOPE contribute significantly to the total health care expenditure in rheumatoid arthritis. The patient perspective has to be taken into account when calculating the overall direct costs of rheumatoid arthritis from a societal point of view.
Easy dye application at surveillance colonoscopy: modified use of a washing pump
Authors: Z. P. Tsiamoulos, B. P. Saunders
Journal: Gut (2011)

Pan-colonic chromo-endoscopy appears to enhance the detection of subtle colonic lesions such as flat adenomas and dysplasia-associated lesions/masses (DALMs) in patients undergoing surveillance colonoscopy.1 Recent British Society of Gastroenterology guidelines now recommend pan-colonic dye spray during colonoscopy for ulcerative colitis surveillance.2

A practical drawback to the use of pan-colonic dye …
C-Reactive Protein and Complement Are Important Mediators of Tissue Damage in Acute Myocardial Infarction
Authors: M. Griselli, J. Herbert, W.L. Hutchinson, K.M. Taylor, M. Sohail, T. Krausz, M.B. Pepys
Journal: The Journal of Experimental Medicine (1999)

Myocardial infarction in humans provokes an acute phase response, and C-reactive protein (CRP), the classical acute phase plasma protein, is deposited together with complement within the infarct. The peak plasma CRP value is strongly associated with postinfarct morbidity and mortality. Human CRP binds to damaged cells and activates complement, but rat CRP does not activate complement. Here we show that injection of human CRP into rats after ligation of the coronary artery reproducibly enhanced infarct size by approximately 40%. In vivo complement depletion, produced by cobra venom factor, completely abrogated this effect. Complement depletion also markedly reduced infarct size, even when initiated up to 2 h after coronary ligation. These observations demonstrate that human CRP and complement activation are major mediators of ischemic myocardial injury and identify them as therapeutic targets in coronary heart disease.
Effect of Intravenous Ascorbic Acid Medication on Serum Levels of Soluble Transferrin Receptor in Hemodialysis Patients
Authors: Der-Cherng Tarng, Szu-Chun Hung, Tung-Po Huang
Journal: Journal of the American Society of Nephrology (2004)

ABSTRACT. Intravenous ascorbic acid (IVAA) medication has been shown to facilitate iron release from inert depots and subsequently circumvent the defective iron utilization in chronic hemodialysis (HD) patients who are treated with recombinant human erythropoietin (rHuEPO). This study focuses on the effects of IVAA supplementation on serum concentrations of soluble transferrin receptors (TfR) on the basis of the hypothesis that an increase of labile iron in the cytosol will lead to inhibition of TfR expression. First, 138 HD patients were studied to evaluate the interrelation between serum TfR and iron status. In a stepwise multivariate analysis, serum EPO and transferrin saturation (TSAT) were the two independent predictors for serum TfR in HD patients (r2 = 0.510, P < 0.001). Further analyses showed that the lower the serum EPO and the higher the TSAT, the lower the serum TfR in HD patients who are on maintenance rHuEPO treatment. Second, 36 HD patients were recruited in a randomized, controlled study to receive IVAA (total dose of 2000 mg) or normal saline (placebo) medication. Serum levels of TfR, EPO, and ferritin and TSAT were measured at baseline and within 7 d after starting IVAA or placebo. There were no significant changes in serum EPO and ferritin levels in patients who received either IVAA (n = 18) or placebo (n = 18). Serum TfR levels (P < 0.001) significantly declined with a parallel rise in TSAT (P < 0.05) as compared with presupplemental values within 7 d in IVAA patients before any apparent alteration in hematocrit values, but the changes were not observed in the placebo group. The trend of decreased serum TfR and increased TSAT was similar in IVAA patients with ferritin of <500 μg/L or >500 μg/L. It is concluded that ascorbic acid status can significantly decrease serum TfR concentrations and increase percentage of TSAT, probably through alterations in intracellular iron metabolism.
Genetic vs Environmental Factors That Correlate With Rosacea
Authors: Nely Aldrich, Meg Gerstenblith, Pingfu Fu, Marie S. Tuttle, Priya Varma, Erica Gotow, Kevin D. Cooper, Margaret Mann, Daniel L. Popkin
Journal: JAMA Dermatology (2015)

To our knowledge, this is the first study on rosacea to formally define genetic and environmental contributions.To study a cohort of identical and fraternal twins to determine whether genetic factors contribute to rosacea development and, if genetic factors are present, quantitatively estimate the genetic contribution, as well as to identify environmental factors that correlate with rosacea by controlling for genetic susceptibility.Identical and fraternal twins were surveyed regarding risk factors implicated in rosacea. Faculty dermatologists determined a rosacea score for each twin participant according to the National Rosacea Society (NRS) grading system. Data were collected at the annual Twins Days Festival in Twinsburg, Ohio, on August 4-5, 2012, and August 2-3, 2013. Analysis was conducted for several months after each meeting. A cohort of 550 twin individuals, with most from Ohio, Pennsylvania, and the northeastern United States, participated.The NRS score and rosacea subtype were assessed using the NRS grading system and physical examination by board-certified dermatologists.Among the 275 twin pairs (550 individuals), there were 233 identical twin pairs with a mean rosacea score of 2.46 and 42 fraternal twin pairs with a mean rosacea score of 0.75. We observed a higher association of NRS scores between identical vs fraternal twins (r = 0.69 vs r = 0.46; P = .04), demonstrating a genetic contribution. Using the ACE model (proportion of variance in a trait heritable secondary to additive genetics [A] vs the proportions due to a common environment [C] and unique environment [E]), we calculated this genetic contribution to be 46%. A higher NRS score was also significantly associated with the following factors: age (r = 0.38; P < .001) and lifetime UV radiation exposure (r = 0.26; P < .001). These associations remained after use of propensity score matching to adjust for multicollinearity. Other correlated variables included body mass index (r = 0.21; P < .001), smoking (r = 0.10; P < .02), alcohol consumption (r = 0.11; P = .01), cardiovascular comorbidity (r = 0.17; P < .001), and skin cancer comorbidity (r = 0.19; P < .001).The study of twins allows us to separate genetic susceptibility and the influence of environmental factors affecting rosacea. We found that approximately half of the contribution to the NRS score could be accounted for by genetics and the other half by environment. We identified correlations between rosacea and UV radiation exposure, alcohol, smoking, skin cancer history, cardiac comorbidity, and age. These findings may help improve current management and expectations of individuals affected by rosacea.
Changes in intramyocardial ST segment voltage and gas tensions with regional myocardial ischemia in the dog.
Authors: S F Khuri, J T Flaherty, J B O'Riordan, B Pitt, R K Brawley, J S Donahoo, V L Gott
Journal: Circulation Research (1975)

This study was designed to evaluate the sensitivity of changes in myocardial carbon dioxide and oxygen tensions as indicators of regional myocardial ischemia and also to determine to what extent these changes can be related to changes in intramyocardial ST segment voltage. Changes in ST segment voltage recorded in unipolar epicardial electrodes proved to be a less-sensitive indicator of underlying myocardial ischemia than were changes in ST segment voltage recorded in unipolar intramyocardial electrodes. In 9 dogs, regional ischemia was produced by placing a variable constrictor on the left circumflex coronary artery; circumflex flow was monitored. Myocardial carbon dioxide and oxygen tensions were measured using a mass spectrometer. Unipolar electrograms were recorded using a multicontact plunge electrode. With progressive degrees of proximal stenosis, ranging from a critical stenosis, which is associated with a decrease in mean flow of less than 15%, to a severe stenosis associated with and 80% decrease, ST voltage increased 21 mv and carbon dioxide tension increased 84 mm Hg, but oxygen tension decreased only 7 mm Hg. The study suggests that increases in intramyocardial ST segment voltage, an index of myocardial ischemia, are associated with parallel increases in myocardial carbon dioxide tension, each providing a more sensitive quantitative correlate of regional myocardial ischemia than do decreases in oxygen tension. The local accumulation of carbon dioxide may be an important pathophysiological mechanism in myocardial ischemia.
HDL induces NO-dependent vasorelaxation via the lysophospholipid receptor S1P3
Authors: Jerzy-Roch Nofer, Markus van der Giet, Markus Tölle, Iza Wolinska, Karin von Wnuck Lipinski, Hideo A. Baba, Uwe J. Tietge, Axel Gödecke, Isao Ishii, Burkhard Kleuser, Michael Schäfers, Manfred Fobker, Walter Zidek, Gerd Assmann, Jerold Chun, Bodo Levkau
Journal: Journal of Clinical Investigation (2004)

HDL is a major atheroprotective factor, but the mechanisms underlying this effect are still obscure. HDL binding to scavenger receptor-BI has been shown to activate eNOS, although the responsible HDL entities and signaling pathways have remained enigmatic. Here we show that HDL stimulates NO release in human endothelial cells and induces vasodilation in isolated aortae via intracellular Ca2+ mobilization and Akt-mediated eNOS phosphorylation. The vasoactive effects of HDL could be mimicked by three lysophospholipids present in HDL: sphingosylphosphorylcholine (SPC), sphingosine-1-phosphate (S1P), and lysosulfatide (LSF). All three elevated intracellular Ca2+ concentration and activated Akt and eNOS, which resulted in NO release and vasodilation. Deficiency of the lysophospholipid receptor S1P3 (also known as LPB3 and EDG3) abolished the vasodilatory effects of SPC, S1P, and LSF and reduced the effect of HDL by approximately 60%. In endothelial cells from S1P3-deficient mice, Akt phosphorylation and Ca2+ increase in response to HDL and lysophospholipids were severely reduced. In vivo, intra-arterial administration of HDL or lysophospholipids lowered mean arterial blood pressure in rats. In conclusion, we identify HDL as a carrier of bioactive lysophospholipids that regulate vascular tone via S1P3-mediated NO release. This mechanism may contribute to the vasoactive effect of HDL and represent a novel aspect of its antiatherogenic function.
Human Genetic Variation Influences Vitamin C Homeostasis by Altering Vitamin C Transport and Antioxidant Enzyme Function
Authors: Alexander J. Michels, Tory M. Hagen, Balz Frei
Journal: Annual Review of Nutrition (2013)

New evidence for the regulation of vitamin C homeostasis has emerged from several studies of human genetic variation. Polymorphisms in the genes encoding sodium-dependent vitamin C transport proteins are strongly associated with plasma ascorbate levels and likely impact tissue cellular vitamin C status. Furthermore, genetic variants of proteins that suppress oxidative stress or detoxify oxidatively damaged biomolecules, i.e., haptoglobin, glutathione-S-transferases, and possibly manganese superoxide dismutase, affect ascorbate levels in the human body. There also is limited evidence for a role of glucose transport proteins. In this review, we examine the extent of the variation in these genes, their impact on vitamin C status, and their potential role in altering chronic disease risk. We conclude that future epidemiological studies should take into account genetic variation in order to successfully determine the role of vitamin C nutriture or supplementation in human vitamin C status and chronic disease risk.