tbuckley/cabot-search huggingface dataset:
Abstract IA22: Cancer as a single process of a dysregulated epigenome
Authors: Andrew P. Feinberg
Journal: Cancer Research (2013)

Abstract Since the discovery of altered DNA methylation in cancer in 1982, most studies of cancer epigenetics have focused on epimutations which could serve as surrogates of mutation. In the past decade, we and our collaborators have been leading efforts to develop whole genome approaches to epigenetic analysis of human disease, that include novel approaches to array-based analysis and whole genome bisulfite sequencing. This has led to the first whole genome bisulfite sequencing methylation map of the cancer genome. Surprising results have been the discovery of CpG island shores and large hypomethylated blocks corresponding to nuclear lamina / heterochromatin regions, and accounting for the vast majority of epigenetic changes in cancer. These results point to the possibility that at least solid tumors represent epigenetically a single process with common molecular characteristic, namely increased epigenetic plasticity that allows selection of the tumor cells at the expense of the host. This view can explain most of the hallmarks of cancer, as well as offering a strategy for powerful new approaches to risk detection and treatment. Citation Format: Andrew P. Feinberg. Cancer as a single process of a dysregulated epigenome. [abstract]. In: Proceedings of the AACR Special Conference on Chromatin and Epigenetics in Cancer; Jun 19-22, 2013; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2013;73(13 Suppl):Abstract nr IA22.
The critical role of tissue angiotensin-converting enzyme as revealed by gene targeting in mice.
Authors: C R Esther, E M Marino, T E Howard, A Machaud, P Corvol, M R Capecchi, K E Bernstein
Journal: Journal of Clinical Investigation (1997)

Angiotensin-converting enzyme (ACE) generates the vasoconstrictor angiotensin II, which plays a critical role in maintenance of blood pressure in mammals. Although significant ACE activity is found in plasma, the majority of the enzyme is bound to tissues such as the vascular endothelium. We used targeted homologous recombination to create mice expressing a form of ACE that lacks the COOH-terminal half of the molecule. This modified ACE protein is catalytically active but entirely secreted from cells. Mice that express only this modified ACE have significant plasma ACE activity but no tissue-bound enzyme. These animals have low blood pressure, renal vascular thickening, and a urine concentrating defect. The phenotype is very similar to that of completely ACE-deficient mice previously reported, except that the renal pathology is less severe. These studies strongly support the concept that the tissue-bound ACE is essential to the control of blood pressure and the structure and function of the kidney.
Responsiveness and variability of airflow obstruction in chronic obstructive pulmonary disease. Clinicopathologic correlative studies.
Authors: A Nagai, W M Thurlbeck, K Konno
Journal: American Journal of Respiratory and Critical Care Medicine (1995)

We have studied the relationships between pulmonary lesions and bronchodilator response and variability of FEV1 in 41 patients enrolled in the National Institutes of Health Intermittent Positive Pressure Breathing Trial who died, came to autopsy, and provided adequate tissue to quantitate lesions. The patients had moderate to severe chronic airflow obstruction and various degrees of response to 250 micrograms isoproterenol inhalation. Airway responsiveness was positively correlated with bronchial eosinophilia, bronchial inflammation, and bronchiolar fibrosis, and it was negatively correlated with bronchiolar goblet cell metaplasia and emphysema. Patients with an increase of 190 ml or more in FEV1 after bronchodilator had less bronchial cartilage and less goblet metaplasia in bronchioles. Airway smooth muscle was not related to airway responsiveness and variability. Flow rates were adversely affected by bronchial eosinophilia for given emphysema scores. This study shows the importance of the eosinophil as part of chronic nonspecific lung disease. Lack of airway responsiveness was associated with lesions such as emphysema and goblet cell metaplasia, which by themselves cause severe chronic airflow obstruction. The better-preserved lung function in patients with increased airway responsiveness is attributed to negative correlations with emphysema and positive correlations with bronchial eosinophilia.
MALIGNANT DIPHTHERIA AND THE IMMUNIZING POWER OF ANTITOXIN.
Authors: J. SPENCER PURDY
Journal: JAMA (1907)

<h3>History.</h3> —C. M., male, aged 13, developed diphtheria which was diagnosed as such April 11. On the afternoon of April 10, though the throat was most carefully examined, no membrane could be discovered. The following morning, however, it covered the tonsils, posterior pharynx, uvula and nasal cavity. The attack was apparently a most malignant one, cultures of pure growth of the Klebs-Loeffler bacillus being made from swabs of the nose and throat. On the night of April 12, the patient, while in a critical condition, was kissed by the three other children in the family and also by his parents; this in the face of severe opposition on the part of the attending physicians. The patient died April 13, having previously received 60,000 units of diphtheria antitoxin. The rest of the family developed diphtheria on April 13 and 14, 3 of the 5 members having received on April 11, 500
New Observations on Distribution of Neoplasms of Female Breast in Certain European Countries
Authors: A. J. Lea
Journal: BMJ (1965)

Sodium Fluoride and Cell Growth-Armstrong et al.EDIiRNUHL 0.45 and 0.48 p.p.m. after 33 and 34 weeks of continued treat- ment.It seems certain, then, that the fluid environment of cells cannot reach the fluoride concentrations which are required to inhibit cell growth of those cells that have been studied under in vitro conditions. SummarySodium fluoride was added in known amounts to cultures of HeLa and human oesophageal cells, and the multiplication of the cells was determined by cell counts carried out by an operator who was unaware of the fluoride contents of the media.Amounts of added fluoride up to 4.5 p.p.m. did not affect the multiplication of HeLa cells when the fluoride was added to the media at the same time as the media were inoculated with the cells.No effect on cell multiplication or on protein synthesis was fcund by up to 10 p.p.m. added fluoride with HeLa cells or oesophageal cells.At 15 p.p.m. added fluoride an incipient retardant effect on growth of oesophageal epithelial cells was noted.These results indicate that higher fluoride concentrations than those found in human body fluids are required, under in vitro conditions, to alter epithelial cell growth.
Effect of cisapride on the gastrointestinal transit of a solid meal in normal human subjects.
Authors: C A Edwards, S Holden, C Brown, N W Read
Journal: Gut (1987)

The effect of cisapride, a new gastrointestinal prokinetic agent, on the transit of a standard meal through the stomach, small intestine and colon was studied in 10 normal subjects. Cisapride had no significant effect on gastric emptying but decreased mouth to caecum transit time (p less than 0.01). Stool weight and frequency were not significantly increased but the time for the first appearance of stool markers and the arrival of 20% and 50% of stool markers was decreased after cisapride (p less than 0.05).
Graham George Haigh
Authors: Gordon Cameron
Journal: BMJ (2004)

Former general practitioner Hull, East Yorkshire (b Cudworth, South Yorkshire, 1929; q Leeds 1954; MRCGP, AFOM), died from carcinomatosis on 3 September 2004.​2004.




Figure 1




After two years' national service Graham served in the Territorial Army for 10 years. He was a medical officer to St John Ambulance Association for 37 years, being admitted to the Order of St John of Jerusalem in 1985. He was a GP trainer and was also industrial medical officer to several factories and commercial concerns. Graham gave unstinting time to children's homes and to the Hull and East Riding branch of the BMA, becoming president. He leaves a wife, Kay; three children; and five grandchildren.
Child Development: Analysis and Synthesis
Authors: Stuart M. Finch
Journal: JAMA (1977)

Written by a pediatrician, this book covers various aspects of the child's development from infancy through adolescence. It is divided into three parts, "The World of Children as Seen by Adults," "The World as Seen Through the Eyes of Children," and "Synthesis." Part 1 contains material on neurological aspects and a good summary of various schools of thought such as those pioneered by Freud, Piaget, Erikson, and Luquet. Since the author has a special interest in children's drawings, the book has many illustrations as they relate to neurological, emotional, and cognitive phases. He stresses the need to allow children to enjoy expression through art. He believes that all too often adults intrude too early with attempts to teach, and thus they destroy spontaneity. One of several excellent chapters in part 2 is the section on creativity, where the author writes: "The creativity in every child should find encouragement during these
Recurrent acute thrombocytopenia in the hospitalized patient: Sepsis, DIC, HIT, or antibiotic‐induced thrombocytopenia
Authors: Talla A. Rousan, Ibrahim T. Aldoss, Benjamin D. Cowley, Brian R. Curtis, Daniel W. Bougie, Richard H. Aster, James N. George
Journal: American Journal of Hematology (2009)

A physician or group of physicians considers presentation and evolution of a real clinical case, reacting to clinical information and data (boldface type).This is followed by a discussion/commentary.
Legionnaires' disease. A cause of lung abscess
Authors: K. K. Venkatachalam
Journal: JAMA (1979)

LEGIONNAIRES' disease can occur in both epidemic and sporadic forms, and the clinical manifestations may range from asymptomatic infection to fulminant pneumonia.<sup>1</sup>We report a case of lung abscess from the Legionnaires' bacterium occurring in a renal homograft recipient. <h3>Report of a Case</h3> A 32-year-old woman who had been receiving long-term hemodialysis for four years for chronic renal failure secondary to nephrosclerosis received her second cadaver kidney transplant in November 1977. Immunosuppression consisted initially of azathioprine, 2.5 mg/kg of body weight, and methylprednisolone, 1.2 mg/kg of body weight. Four courses of antirejection therapy, each consisting of 1 g of methylprednisolone intravenously daily for three days, were given during a one-month period. The kidney was removed 34 days after transplantation, due to irreversible rejection. Azathioprine therapy was discontinued, and the dosage of methylprednisolone was halved to 24 mg/day on the day of transplant nephrectomy. She had been afebrile during the
IgA nephropathy in non-cirrhotic portal hypertension.
Authors: C Babbs, T W Warnes, H B Torrance, F W Ballardie
Journal: Gut (1991)

Renal glomerular changes are a well recognised complication of cirrhosis and are frequently characterised by mesangial IgA deposition. We report a patient with non-cirrhotic portal hypertension who developed IgA nephropathy and a nephrotic syndrome with renal histological changes classically associated with cirrhosis. Splenectomy with resection of a splenic artery aneurysm resulted in remission of the nephrotic syndrome. This case illustrates the factors which contribute to the pathogenesis of IgA nephropathy in liver disease.
Chlorpropamide-induced granulomas. A probable hypersensitivity reaction in liver and bone marrow
Authors: Leon A. Rigberg, Morton J. Robinson, Carmelita R. Espiritu
Journal: JAMA (1976)

Anicteric hepatitis, associated with fever and exfoliative dermatitis, developed in a diabetic patient two weeks after intake of a long-acting sulfonylurea, chlorpropamide (Diabinese). Granulomas showing heavy infiltration with eosinophils were found in the liver and bone marrow. These were interpreted as manifestations of an allergic reaction. The clinical signs, abnormal laboratory findings, and hepatic lesions subsided spontaneously on withdrawal of the drug. Bone marrow changes, however, persisted seven months after cessation of the drug. To our knowledge, this is the first report of a patient with liver and bone marrow inflammation characterized by granulomas with eosinophilic infiltration following intake of chlorpropamide. (<i>JAMA</i>235:409-410, 1976)
Complex of Meningococcal Group B Polysaccharide and Type 2 Outer Membrane Protein Immunogenic in Man
Authors: W. D. Zollinger, R. E. Mandrell, J. M. Griffiss, P. Altieri, S. Berman
Journal: Journal of Clinical Investigation (1979)

A noncovalent complex of meningococcal group B polysaccharide and type 2 outer membrane protein has been characterized and its potential as a vaccine against group B meningococcal disease investigated. The polysaccharide component was found to have a partition coefficient, K(d), of 0.34 on Sepharose CL-4B in the presence of sodium deoxycholate. The protein consisted of four to five major proteins including the principal outer membrane protein. Hydrophobic binding between the protein and polysaccharide was demonstrated by gel filtration and isopycnic CsCl density gradient centrifugation and found to involve all of the proteins. After demonstrating safety and immunogenicity in animals, two lots of vaccine were tested in a total of eight volunteers. Two 120-mug doses were given subcutaneously at 0 and 5 wk. Mild local reactions occurred in all eight volunteers, but no systemic reactions were observed. 2 wk after the first dose, six of the volunteers had increased levels of bactericidal antibodies against both the group B polysaccharide and the outer membrane proteins. Antibody rises to the group B polysaccharide (mean 6-fold) were confirmed by passive hemagglutination assays and rises to the proteins (mean 10-fold) by a solid phase radioimmunoassay. The second dose resulted in little or no increase in antibody titers. Antibody titers declined over a period of 14 wk but mostly remained above preimmunization levels. Bactericidal antibodies with specificity for the group B polysaccharide were mostly of the immunoglobulin (Ig)M class, and were directed against a determinant associated only with high molecular weight polysaccharides. We conclude that both the group B polysaccharide and the outer membrane protein are immunogenic in man when presented as a complex and that the complex warrants further testing and development as a vaccine against group B meningococcal disease.
INFLUENZA VIRUS MULTIPLICATION IN THE CHORIOALLANTOIC MEMBRANE IN VITRO: KINETIC ASPECTS OF INHIBITION BY 5, 6-DICHLORO-1-ß-D-RIBOFURANOSYLBENZIMIDAZOLE
Authors: Igor Tamm, David A. J. Tyrrell
Journal: The Journal of Experimental Medicine (1954)

A procedure is described for kinetic studies on the multiplication of Lee virus in the chorioallantoic membrane in vitro employing the hemagglutination technique for measurement of virus concentration. A linear relationship was found between the logarithm of virus adsorbed and the amount of membrane used. Of the virus adsorbed less than 10 per cent could be recovered from the membrane. Of the recoverable virus 90 per cent was eliminated by specific immune serum. Lee virus was adsorbed by the allantoic and chorionic layers of the membrane to a similar degree. Multiplication occurred in both layers and to a similar extent. When 10(7.66) EID(50) of Lee virus was inoculated per 2.9 cm.(2) of chorioallantoic membrane, the ratio of infectivity to hemagglutination titer in the yield was low, although the rate of appearance of virus particles was not diminished despite the large inocula. Virus produced in membranes was liberated rapidly and continually into the medium. 5,6-Dichloro-1-beta-D-ribofuranosylbenzimidazole (DRB), 0.000055 M, prolonged the latent period by more than 100 per cent. The rate of increase during the period of rapid rise was similar in the presence or absence of DRB, but the yield was markedly reduced at the end of this period in the presence of DRB. The amount of the virus in the membranes continued to rise in the presence of DRB and eventually approached the maximal levels reached much earlier in the controls. Measurement of the amount of virus in the media indicated a greater degree of inhibition than did measurement in the membranes. Comparative studies with two benzimidazole derivatives on the dependence of the inhibitory effect on the time of addition of the compound showed that processes which could be inhibited by DRB were of shorter duration than those inhibited by 2,5-dimethylbenzimidazole (MB). With MB the relationship between the time of addition and the inhibitory effect was similar both for virus and for soluble complement-fixing antigen; with DRB the inhibitable processes were of shorter duration for the complement-fixing antigen than for virus particles. DRB was not only 35 times more active on a molar basis but also was more selective in its action than MB. DRB interfered with processes which preceded the emergence of either soluble complement-fixing antigen or virus particles. Some of the implications of these findings are discussed in relation to the mechanism of inhibition of influenza virus multiplication by benzimidazole derivatives.
FRI0079 Rheumatoid factor as predictor of response to non TNF antagonist biologic therapies in rheumatoid arthritis: Systematic review and meta-analysis
Authors: J.R. Maneiro, E. Salgado, L. Carmona, J.J. Gomez-Reino
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Currently, are searching for biomarkers to predict response to biological therapies and select patients with better response to each of them. <h3>Objectives</h3> To identify if rheumatoid factor (RF) is predictor of response to rituximab (RTX), abatacept (ABT), and tocilizumab (TCZ) in rheumatoid arthritis (RA). <h3>Methods</h3> Systematic review and meta-analysis of clinical trials and observational studies based on a sensitive search. Meta-regression was used to explore causes of heterogeneity. Unpublished data of clinical trials provided by the authors were also included. <h3>Results</h3> The electronic search captured 3221 references and 422 meeting abstracts. By hand search, four additional articles were also identified. A total of 23 studies meet the purpose of the study and were included in the review. RF positivity at starting predicts better ACR20 [OR, 1.95 (1.24, 3.08)], ACR50 [OR, 5.38 (2.50, 11.60)] and EULAR response [OR, 3.52 (1.66, 7.45)] in 14 studies with RTX (Figure 1), and better ACR20 [OR, 1.51 (1.21, 1.90)] in 6 studies with TC. In 3 studies with ABT, no association was found between response and RF [OR 1.36 (0.97, 1.90)]. No asymmetries in the funnel plots or significant variables were found in the meta-regression. <h3>Conclusions</h3> In RA, RF positivity predicts better response to RTX and TCZ but not to ABT. <h3>Disclosure of Interest</h3> J. R. Maneiro: None Declared, E. Salgado: None Declared, L. Carmona Speakers Bureau: L.C. has received lecture fees from Abbott and Pfizer, J. J. Gomez-Reino Grant/Research support from: JJ.G-R has received research grants from Roche and Schering-Plough, Consultant for: JJ.G-R is on the Advisory Boards of BMS, Pfizer, Roche, Schering-Plough and UCB SA, Speakers Bureau: JJ.G-R has received lecture fees from, BMS, Roche, Schering-Plough and Wyeth
Hypersplenism induced by splenic vein ligation
Authors: Brian Garibaldi, Karen E. King, Julie M. Jaffe, Alison R. Moliterno
Journal: American Journal of Hematology (2007)

Abstract Warm autoimmune hemolytic anemia (AIHA) is a rare clinical entity. It is usually caused by an IgG autoantibody directed against the red blood cell membrane that causes extravascular hemolysis predominantly in the spleen. As a result, disease states or procedures that result in hypersplenism would be expected to increase red cell destruction in patients with an underlying warm AIHA. We present the case of a patient with a previously undiagnosed warm AIHA, who developed worsening hemolysis after undergoing splenic vein ligation during a pancreaticoduodenectomy to remove a neuroendocrine tumor. Am. J. Hematol., 2008. © 2007 Wiley‐Liss, Inc.
Abstract 5583: Clinical Characteristics and Outcomes of Acute Myocardial Infarction Patients with Previous Cerebrovascular Diseases
Authors: Yong Jian Li, Seung Woon Rha, Kang Yin Chen, Kanhaiya L Poddar, Jae Hyoung Park, Jin Oh Na, Cheol Ung Choi, Hong Euy Lim, Jin Won Kim, EungJu Kim, Chang Gyu Park, Hong Seog Seo, DongJoo Oh, Myung Ho Jeong, Youngkeun Ahn
Journal: Circulation (2008)

Background: Cerebrovascular disease (CVD) can be an important future cardiovascular event. The impact of previous cerebrovascular disease (CVD) on the clinical characteristics and midterm outcomes of patients (pts) with acute myocardial infarction (AMI) has not been well described in Asian population. Methods: Data were analyzed from 8151 pts with AMI (either STEMI or NSTEMI) enrolled in Korea Acute Myocardial Infarction Registry (KAMIR) from 2005 to 2007. Results: Of 8151 pts, 552 pts (6.8%) had previous CVD. The pts with CVD were older (68.95 ± 10.11 vs 62.83 ± 12.74, P &lt;0.001), more incidence in women (70.4% vs 62.7%, P &lt;0.001), showed higher incidence of hypertension and diabetes than the pts without CVD. The pts with previous CVD presented more often with NSTEMI and higher Killip class than the pts without CVD. Further, pts with CVD received less percutaneous coronary intervention (PCI) or thrombolysis compared with the pts without CVD. Intensive medical therapy was equally maintained in both groups. Pts with CVD showed higher incidences of cardiac death [13.6% vs 5.1%, adjusted odd ratio (OR) 2.11, 95% confidence interval (CI) 1.60 –2.79, P &lt;0.001], total death (15.9% vs 5.9%, adjusted OR 2.15; 95% CI 1.65–2.80, P &lt;0.001) and total major adverse cardiac events (MACE, 23.0% vs 11.6%, adjusted OR 1.45; 95% CI 1.14 –1.85, P =0.003) at 8 months. The incidences of recurrent MI and repeat revascularization at 8 months were similar between the two groups. Conclusions: Pts with CVD showed more severe and worse clinical characteristics on admission and was associated with lower rates of PCI or thrombolysis. When we consider the poorer midterm clinical outcomes including higher mortality and MACE, in pts with prior CVD, more intensive and aggressive management for this particular subset of pts should be emphasized for better long-term clinical outcomes.
Hereditary xanthinuria. Evidence for enhanced hypoxanthine salvage.
Authors: F A Mateos, J G Puig, M L Jiménez, I H Fox
Journal: Journal of Clinical Investigation (1987)

We tested the hypothesis that there is an enhanced rate of hypoxanthine salvage in two siblings with hereditary xanthinuria. We radiolabeled the adenine nucleotide pool with [8-14C]adenine and examined purine nucleotide degradation after intravenous fructose. The cumulative excretion of radioactivity during a 5-d period was 9.7% and 9.1% of infused radioactivity in the enzyme-deficient patients and 6.0 +/- 0.7% (mean +/- SE) in four normal subjects. Fructose infusion increased urinary radioactivity to 7.96 and 9.16 X 10(6) cpm/g creatinine in both patients and to 4.73 +/- 0.69 X 10(6) cpm/g creatinine in controls. The infusion of fructose increased total urinary purine excretion to a mean of 487% from low-normal baseline values in the patients and to 398 +/- 86% in control subjects. In the enzyme-deficient patients, the infusion of fructose elicited an increase of plasma guanosine from undetectable values to 0.7 and 0.9 microM. With adjustments made for intestinal purine loss, these data support the hypothesis that there is enhanced hypoxanthine salvage in hereditary xanthinuria. Degradation of guanine nucleotides to xanthine bypasses the hypoxanthine salvage pathway and may explain the predominance of this urinary purine compound in xanthinuria.