tbuckley/cabot-search huggingface dataset:
Thiodiglycolic acid and dermatological reactions following<i>S</i>-carboxymethyl-<scp>l</scp>-cysteine administration
Authors: G.B. Steventon, S.C. Mitchell
Journal: British Journal of Dermatology (2005)

Journal Article Thiodiglycolic acid and dermatological reactions following S‐carboxymethyl‐l‐cysteine administration Get access G.B. Steventon, G.B. Steventon Pharmaceutical Sciences Research Division, School of Biomedical and Health Sciences, King's College London, London SE1 9NH, U.K. Section of Biological Chemistry, Division of Biomedical Sciences, Faculty of Life Sciences, Imperial College London, London SW7 2AZ, U.K. E‐mail: glyn.steventon@kcl.ac.uk Search for other works by this author on: Oxford Academic Google Scholar S.C. Mitchell S.C. Mitchell Pharmaceutical Sciences Research Division, School of Biomedical and Health Sciences, King's College London, London SE1 9NH, U.K. Section of Biological Chemistry, Division of Biomedical Sciences, Faculty of Life Sciences, Imperial College London, London SW7 2AZ, U.K. E‐mail: glyn.steventon@kcl.ac.uk Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 154, Issue 2, 1 February 2006, Pages 386–387, https://doi.org/10.1111/j.1365-2133.2005.07051.x Published: 01 February 2006
Global Quantitative Phosphoproteome Analysis of Human Tumor Xenografts Treated with a CD44 Antagonist
Authors: Stefan Weigand, Frank Herting, Daniela Maisel, Adam Nopora, Edgar Voss, Christoph Schaab, Martin Klammer, Andreas Tebbe
Journal: Cancer Research (2012)

The cell surface glycoprotein CD44 plays an important role in the development and progression of various tumor types. RG7356 is a humanized antibody targeting the constant region of CD44 that shows antitumor efficacy in mice implanted with CD44-expressing tumors such as MDA-MB-231 breast cancer cells. CD44 receptor seems to function as the main receptor for hyaluronic acid and osteopontin, serving as coreceptor for growth factor pathways like cMet, EGFR, HER-2, and VEGFR and by cytoskeletal modulation via ERM and Rho kinase signaling. To assess the direct impact of RG7356 binding to the CD44 receptor, a global mass spectrometry-based phosphoproteomics approach was applied to freshly isolated MDA-MB-231 tumor xenografts. Results from a global phosphoproteomics screen were further corroborated by Western blot and ELISA analyses of tumor lysates from CD44-expressing tumors. Short-term treatment of tumor-bearing mice with RG7356 resulted in modifications of the MAPK pathway in the responsive model, although no effects on downstream phosphorylation were observed in a nonresponsive xenograft model. Taken together, our approach augments the value of other high throughput techniques to identify biomarkers for clinical development of targeted agents.
Bronchodilator response in the lung health study over 11 yrs
Authors: N. R. Anthonisen, P. G. Lindgren, D. P. Tashkin, R. E. Kanner, P. D. Scanlon, J. E. Connett
Journal: European Respiratory Journal (2005)

Long-term changes in bronchodilator response in people with mild chronic obstructive pulmonary disease were assessed in this study. Changes in forced expiratory volume in one second (FEV 1 ) in response to isoproterenol was measured in 4,194 participants in the Lung Health Study annually for 5 yrs, and again 11 yrs after study entry. Responses were quantitated in terms of mL (absolute), as per cent of the pre-bronchodilator value (relative), and as a per cent of the predicted normal value (% predicted). At baseline, the mean pre-bronchodilator FEV 1 was 75.4% predicted, and responses were small. Relative and percentage predicted responses were similar in males and females; and correlated positively with methacholine reactivity, and negatively with smoking intensity and age. Baseline bronchodilator responses did not correlate with subsequent decline in FEV 1 . There was a substantial increase in response over the first year of the study, largely due to smoking cessation, with larger increases in those who stopped smoking. After the first year absolute responses changed little in those who maintained smoking cessation, but increased in those who did not. Mean relative and percentage predicted responses increased in all participants throughout the study. There was substantial annual variability of absolute response, and it was poorly reproducible in individual participants. In conclusion, smoking cessation increased bronchodilator response, and response did not predict the rate of decline of forced expiratory volume in one second.
A large-scale, multicentre, double-blind trial of ursodeoxycholic acid in patients with chronic hepatitis C
Authors: M. Omata, H. Yoshida, J. Toyota, E. Tomita, S. Nishiguchi, N. Hayashi, S. Iino, I. Makino, K. Okita, G. Toda, K. Tanikawa, H. Kumada
Journal: Gut (2007)

Combined pegylated interferon and ribavirin has improved chronic hepatitis C (CH-C) therapy; however, sustained virological response is achieved in only about half of the patients with a 1b genotype infection. We assessed oral ursodeoxycholic acid (UDCA) on serum biomarkers as a possible treatment for interferon non-responders.CH-C patients with elevated alanine aminotransferase (ALT) were assigned randomly to 150 (n = 199), 600 (n = 200) or 900 mg/day (n = 197) UDCA intake for 24 weeks. Changes in ALT, aspartate aminotransferase (AST) and gamma-glutamyl transpeptidase (GGT) were assessed. This study is registered at ClinicalTrial.gov, identifier NCT00200343.ALT, AST and GGT decreased at week 4 and then remained constant during drug administration. The median changes (150, 600 and 900 mg/day, respectively) were: ALT, -15.3, -29.2 and -36.2%; AST, -13.6, -25.0 and -29.8%; GGT, -22.4, -41.0 and -50.0%. These biomarkers decreased significantly less in the 150 mg/day than in the other two groups. Although changes in ALT and AST did not differ between the 600 and 900 mg/day groups, GGT was significantly lower in the 900 mg/day group. In subgroup analysis, ALT decreased significantly in the 900 mg/day group when the baseline GGT exceeded 80 IU/l. Serum HCV-RNA did not change in any group. Adverse effects were reported by 19.1% of the patients, with no differences between groups.A 600 mg/day UDCA dose was optimal to decrease ALT and AST levels in CH-C patients. The 900 mg/day dose decreased GGT levels further, and may be preferable in patients with prevailing biliary injuries.
High-Density Single Nucleotide Polymorphism Array Defines Novel Stage and Location-Dependent Allelic Imbalances in Human Bladder Tumors
Authors: Karen Koed, Carsten Wiuf, Lise-Lotte Christensen, Friedrik P. Wikman, Karsten Zieger, Klaus Møller, Hans von der Maase, Torben F. Ørntoft
Journal: Cancer Research (2005)

Bladder cancer is a common disease characterized by multiple recurrences and an invasive disease course in more than 10% of patients. It is of monoclonal or oligoclonal origin and genomic instability has been shown at certain loci. We used a 10,000 single nucleotide polymorphism (SNP) array with an average of 2,700 heterozygous SNPs to detect allelic imbalances (AI) in 37 microdissected bladder tumors from 17 patients. Eight tumors represented upstaging from Ta to T1, eight from T1 to T2+, and one from Ta to T2+. The AI was strongly stage-dependent as four chromosomal arms showed AI in > 50% of Ta samples, eight in T1, and twenty-two in T2+ samples. The tumors showed stage-dependent clonality as 61.3% of AIs were reconfirmed in later T1 tumors and 84.4% in muscle-invasive tumors. Novel unstable chromosomal areas were identified at chromosomes 6q, 10p, 16q, 20p, 20q, and 22q. The tumors separated into two distinct groups, highly stable tumors (all Ta tumors) and unstable tumors (2/3 muscle-invasive). All 11 unstable tumors had lost chromosome 17p areas and 90% chromosome 8 areas affecting Netrin-1/UNC5D/MAP2K4 genes as well as others. AI was present at the TP53 locus in 10 out of 11 unstable tumors, whereas 6 had homozygous TP53 mutations. Tumor distribution pattern reflected AI as seven out of eight patients with additional upper urinary tract tumors had genomic stable bladder tumors (P < 0.05). These data show the power of high-resolution SNP arrays for defining clinically relevant AIs.
Release of endothelin from the porcine heart after short term coronary artery occlusion
Authors: T. Tonnessen, P. A Naess, K. A Kirkeboen, J. Offstad, A. Ilebekk, G. Christensen
Journal: Cardiovascular Research (1993)

Journal Article Release of endothelin from the porcine heart after short term coronary artery occlusion Get access Theis Tønnessen, Theis Tønnessen Institute for Experimental Medical Research, University of Oslo, Ullevål Hospital, N-0407 Oslo, Norway: T Tønnesen, P A Naess, K A Kirkebøen, J Offstad, A Ilebekk, G Christensen. Correspondence to Dr Tonnessen. Search for other works by this author on: Oxford Academic PubMed Google Scholar Pål A Naess, Pål A Naess Institute for Experimental Medical Research, University of Oslo, Ullevål Hospital, N-0407 Oslo, Norway: T Tønnesen, P A Naess, K A Kirkebøen, J Offstad, A Ilebekk, G Christensen. Search for other works by this author on: Oxford Academic PubMed Google Scholar Knut A Kirkebøen, Knut A Kirkebøen Institute for Experimental Medical Research, University of Oslo, Ullevål Hospital, N-0407 Oslo, Norway: T Tønnesen, P A Naess, K A Kirkebøen, J Offstad, A Ilebekk, G Christensen. Search for other works by this author on: Oxford Academic PubMed Google Scholar Jon Offstad, Jon Offstad Institute for Experimental Medical Research, University of Oslo, Ullevål Hospital, N-0407 Oslo, Norway: T Tønnesen, P A Naess, K A Kirkebøen, J Offstad, A Ilebekk, G Christensen. Search for other works by this author on: Oxford Academic PubMed Google Scholar Arnfinn Ilebekk, Arnfinn Ilebekk Institute for Experimental Medical Research, University of Oslo, Ullevål Hospital, N-0407 Oslo, Norway: T Tønnesen, P A Naess, K A Kirkebøen, J Offstad, A Ilebekk, G Christensen. Search for other works by this author on: Oxford Academic PubMed Google Scholar Geir Christensen Geir Christensen Institute for Experimental Medical Research, University of Oslo, Ullevål Hospital, N-0407 Oslo, Norway: T Tønnesen, P A Naess, K A Kirkebøen, J Offstad, A Ilebekk, G Christensen. Search for other works by this author on: Oxford Academic PubMed Google Scholar Cardiovascular Research, Volume 27, Issue 8, August 1993, Pages 1482–1485, https://doi.org/10.1093/cvr/27.8.1482 Published: 01 August 1993 Article history Received: 30 December 1992 Accepted: 29 March 1993 Published: 01 August 1993
Sarcoma: concordance between initial diagnosis and centralized expert review in a population-based study within three European regions
Authors: I. Ray-Coquard, M.C. Montesco, J.M. Coindre, A.P. Dei Tos, A. Lurkin, D. Ranchère-Vince, A. Vecchiato, A.V. Decouvelaere, S. Mathoulin-Pélissier, S. Albert, P. Cousin, D. Cellier, L. Toffolatti, C.R. Rossi, J.Y. Blay
Journal: Annals of Oncology (2012)
THE PHYSIOLOGY OF GLOBUS HYSTERICUS
Authors: EDMUND JACOBSON
Journal: JAMA (1924)

It used to be the fashion, when a symptom was found to be functional, to tell the patient that there was nothing the matter with him; he should go home and forget  Nothing anatomically wrong, said the neurologist, and that was all there was to it. But times change, and students are finding that disordered symptoms may be studied scientifically, even in the absence of structural pathologic changes. An interesting example is  hystericus.  The patient has the feeling of a foreign body in his throat, yet none can be found. On examination with proper instruments, nothing wrong is noted in the throat or speech apparatus. A sound passed down the esophagus may meet no unusual resistance, and the esophagus may present nothing more than a little redness or hyperemia (Rosenheim). It is generally agreed that globus occurs not alone in hysterical patients, but in many other conditions as
Observations on the Microcirculation in the Gingiva of Hamsters and Other Laboratory Animals
Authors: P. H. STAPLE, A. L. COPLEY
Journal: Circulation Research (1959)

By using the teeth for immobilisation and employing incident light microscopy at magnifications up to 240x, entire capillary beds could be observed in the labial gingiva in small laboratory animals. In the mandibular incisor region, simple capillary loops, as found in the human gingiva and nail bed, were absent in all species examined except in some guinea pigs. In the hamster, where the topography of the gingival capillary bed was studied in greatest detail, blood flow was regulated by changes in caliber of arterioles; by opening and closing of exits from main capillary channels into networks apparently devoid of vasomotor activity; and by opening and closing of arteriovenous anastomoses. Under certain conditions, settling of blood cells and blood cell clumps to the lower side of gingival veins, together with gravitationally layered flow, was observed.
Identifying the TLR4 bearing target cell in experimental arthritis
Authors: B. T. van den Brand, S. Abdollahi-Roodsaz, M. B. Bennink, O. J. Arntz, W. B. van den Berg, F. A. J. van de Loo
Journal: Annals of the Rheumatic Diseases (2011)

<h3>Purpose</h3> The interleukin 1 (IL-1) receptor antagonist (IL-1Ra) knockout mice spontaneously develop T cell driven arthritis due to excessive IL-1 signalling. Joint destruction is accompanied by increased Th17 cells and elevated IL-17 levels compared to wild type (Balb/c) mice. When cross bred with toll-like receptor 4 (TLR4) knock out (TLR4<sup>−/−</sup>) these animals showed reduced inflammation, joint destruction and diminished IL-17 levels. To reduce adverse effects of TLR4 inhibition a cell specific targeted therapy of arthritis is desired. Therefore, the authors set out to identify the TLR4 bearing cells in experimental arthritis responsible for increased IL-17 production and arthritis severity. <h3>Method</h3> A reciprocal sex-mismatched bone marrow transplantation was performed with TLR4<sup>−/−</sup> and TLR4<sup>+/+</sup> mice in the IL-1Ra<sup>−/−</sup> background and Balb/c bone marrow as control. Y-chromosome staining of bone marrow was performed to assess engraftment. Clinical manifestation of disease was assessed macroscopically over time. Spleen and lymph node cells were isolated and subjected to T helper subset analysis. <h3>Results</h3> Engraftment of bone marrow was near 100% successful as determined by Y-chromosome staining of the bone marrow, which indicates a successful reconstitution. Lack of TLR4 on either the engrafted bone marrow cells or the radio-resistant cells in the joint did not affect disease incidence. However, animals that lacked TLR4 on the engrafted bone marrow derived cells, radio-resistant cells, or both showed reduced macroscopic arthritis scores. In mesenteric lymph nodes there were no differences observed in percentage of interferon γ and IL-17 producing cells. Neither was there a difference in Th1 cells in the spleen. However, decreased Th17 levels were observed in the spleen when radio-resistant cells lack TLR4. <h3>Conclusion</h3> These data suggest that TLR4 plays a role on both the bone marrow derived and local resident cells in aggravating experimental arthritis. TLR4 plays a role locally on the synovial fibroblasts by creating a more aggressive inflammatory environment in the joint cavity and thereby increasing joint destruction. Conversely, TLR4 activation on the bone marrow derived cells could increase T cell activation by antigen presenting cells and thereby promoting a more aggressive Th17 phenotype and increase joint swelling.
Pathogenesis of Liver Fibrosis
Authors: Virginia Hernandez-Gea, Scott L. Friedman
Journal: Annual Review of Pathology Mechanisms of Disease (2011)

Liver fibrosis is a major cause of morbidity and mortality worldwide due to chronic viral hepatitis and, more recently, from fatty liver disease associated with obesity. Hepatic stellate cell activation represents a critical event in fibrosis because these cells become the primary source of extracellular matrix in liver upon injury. Use of cell-culture and animal models has expanded our understanding of the mechanisms underlying stellate cell activation and has shed new light on genetic regulation, the contribution of immune signaling, and the potential reversibility of the disease. As pathways of fibrogenesis are increasingly clarified, the key challenge will be translating new advances into the development of antifibrotic therapies for patients with chronic liver disease.
Estimates of Outcomes Up to Ten Years after Stroke: Analysis from the Prospective South London Stroke Register
Authors: Charles D. A. Wolfe, Siobhan L. Crichton, Peter U. Heuschmann, Christopher J. McKevitt, André M. Toschke, Andy P. Grieve, Anthony G. Rudd
Journal: PLoS Medicine (2011)

Charles Wolfe and colleagues collected data from the South London Stroke Register on 3,373 first strokes registered between 1995 and 2006 and showed that between 20% and 30% of survivors have poor outcomes up to 10 years after stroke.
Atherosclerosis Secondary Prevention Performance Measures After Coronary Bypass Graft Surgery Compared With Percutaneous Catheter Intervention and Nonintervention Patients in the Get With the Guidelines Database
Authors: Loren F. Hiratzka, Kim A. Eagle, Li Liang, Gregg C. Fonarow, Kenneth A. LaBresh, Eric D. Peterson
Journal: Circulation (2007)

The American Heart Association Get With the Guidelines-Coronary Artery Disease program facilitates patient and physician compliance with proven atherosclerosis risk reduction strategies with collaborative learning sessions, teaching materials, predischarge online check lists, and web-based performance measure feedback for continuous quality improvement. Patients having coronary artery bypass graft surgery (CABG) may be subject to different care processes, nursing unit pathways, and personnel than patients having percutaneous catheter intervention or neither intervention, which may affect compliance.The Get With the Guidelines-Coronary Artery Disease database was queried to determine whether compliance with secondary prevention performance measures for CABG patients was different from that for nonsurgical patients. A total of 119,106 patients were treated with CABG (14,118), percutaneous catheter intervention (58,702), or neither intervention (46,286). Compliance with medication prescriptions, including aspirin, beta-blockers, angiotensin-converting enzyme inhibitors, and lipid-lowering drugs, and smoking cessation counseling for eligible patients was analyzed. Medically appropriate exclusions and contraindications were included in the analysis. After adjusting for 14 clinical variables, CABG patients were less likely to receive most secondary prevention measures relative to percutaneous catheter intervention patients. In contrast, CABG patients were more likely to receive aspirin, beta-blocker, and smoking cessation counseling than neither intervention patients. Composite adherence and defect-free rates were highest for percutaneous catheter intervention patients and lowest for neither intervention patients after adjustment.There are significant differences in compliance at hospital discharge with secondary prevention performance measures for CABG patients compared with nonsurgical patients. Process of care differences may explain these differences and should be examined further because significant opportunities for improved compliance are evident. CABG patients in particular represent a group for whom secondary prevention has proven benefits, and they may benefit from future quality improvement interventions.
Lung Adenocarcinoma From East Asian Never-Smokers Is a Disease Largely Defined by Targetable Oncogenic Mutant Kinases
Authors: Yihua Sun, Yan Ren, Zhaoyuan Fang, Chenguang Li, Rong Fang, Bin Gao, Xiangkun Han, Weidong Tian, William Pao, Haiquan Chen, Hongbin Ji
Journal: Journal of Clinical Oncology (2010)

To determine the proportion of lung adenocarcinomas from East Asian never-smokers who harbor known oncogenic driver mutations.In this surgical series, 52 resected lung adenocarcinomas from never-smokers (< 100 cigarettes in a lifetime) at a single institution (Fudan University, Shanghai, China) were analyzed concurrently for mutations in EGFR, KRAS, NRAS, HRAS, HER2, BRAF, ALK, PIK3CA, TP53 and LKB1.Forty-one tumors harbored EGFR mutations, three harbored EML4-ALK fusions, two harbored HER2 insertions, and one harbored a KRAS mutation. All mutations were mutually exclusive. Thus, 90% (47 of 52; 95% CI, 0.7896 to 0.9625) of lung adenocarcinomas from never-smokers were found to harbor well-known oncogenic mutations in just four genes. No BRAF, NRAS, HRAS, or LKB1 mutations were detected, while 15 had TP53 mutations. Four tumors contained PIK3CA mutations, always together with EGFR mutations.To our knowledge, this study represents the first comprehensive and concurrent analysis of major recurrent oncogenic mutations found in a large cohort of lung adenocarcinomas from East Asian never-smokers. Since drugs are now available that target mutant EGFR, HER2, and ALK, respectively, this result indicates that prospective mutation testing in these patients should successfully assign a targeted therapy in the majority of cases.
Mcl-1 Mediates Tumor Necrosis Factor-Related Apoptosis-Inducing Ligand Resistance in Human Cholangiocarcinoma Cells
Authors: Makiko Taniai, Annette Grambihler, Hajime Higuchi, Nate Werneburg, Steve F. Bronk, Daniel J. Farrugia, Scott H. Kaufmann, Gregory J. Gores
Journal: Cancer Research (2004)

Abstract Cholangiocarcinomas are usually fatal neoplasms originating from bile duct epithelia. Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a promising agent for cancer therapy, including cholangiocarcinoma. However, many cholangiocarcinoma cells are resistant to TRAIL-mediated apoptosis. Thus, our aim was to examine the intracellular mechanisms responsible for TRAIL resistance in human cholangiocarcinoma cell lines. Three TRAIL-resistant human cholangiocarcinoma cell lines were identified. All of the cell lines expressed TRAIL receptor 1/death receptor 4 (TRAIL-R1/DR4) and TRAIL-R2/DR5. Expression of TRAIL decoy receptors and the antiapoptotic cellular FLICE-inhibitory protein (cFLIP) was inconsistent across the cell lines. Of the antiapoptotic Bcl-2 family of proteins profiled (Bcl-2, Bcl-xL, and Mcl-1), Mcl-1 was uniquely overexpressed by the cell lines. When small-interfering-RNA (siRNA) technology was used to knock down expression of Bcl-2, Bcl-xL, and Mcl-1, only the Mcl-1-siRNA sensitized the cells to TRAIL-mediated apoptosis. In a cell line stably transfected with Mcl-1-small-hairpin-RNA (Mcl-1-shRNA), Mcl-1 depletion sensitized cells to TRAIL-mediated apoptosis despite Bcl-2 expression. TRAIL-mediated apoptosis in the stably transfected cells was associated with mitochondrial depolarization, Bax activation, cytochrome c release from mitochondria, and caspase activation. Finally, flavopiridol, an anticancer drug that rapidly down-regulates Mcl-1, also sensitized cells to TRAIL cytotoxicity. In conclusion, these studies not only demonstrate that Mcl-1 mediates TRAIL resistance in cholangiocarcinoma cells by blocking the mitochondrial pathway of cell death but also identify two strategies for circumventing this resistance.