tbuckley/cabot-search huggingface dataset:
Reversible LSD1 Inhibition Interferes with Global EWS/ETS Transcriptional Activity and Impedes Ewing Sarcoma Tumor Growth
Authors: Savita Sankar, Emily R. Theisen, Jared Bearss, Timothy Mulvihill, Laura M. Hoffman, Venkataswamy Sorna, Mary C. Beckerle, Sunil Sharma, Stephen L. Lessnick
Journal: Clinical Cancer Research (2014)

Abstract Purpose: Ewing sarcoma is a pediatric bone tumor that absolutely relies on the transcriptional activity of the EWS/ETS family of fusion oncoproteins. While the most common fusion, EWS/FLI, utilizes lysine-specific demethylase 1 (LSD1) to repress critical tumor suppressors, small-molecule blockade of LSD1 has not yet been thoroughly explored as a therapeutic approach for Ewing sarcoma. We therefore evaluated the translational potential of potent and specific LSD1 inhibition with HCI2509 on the transcriptional program of both EWS/FLI and EWS/ERG as well as the downstream oncogenic phenotypes driven by EWS/ETS fusions in both in vitro and in vivo models of Ewing sarcoma. Experimental Design: RNA-seq was used to compare the transcriptional profiles of EWS/FLI, EWS/ERG, and treatment with HCI2509 in both EWS/FLI- and EWS/ERG-containing cell lines. We then evaluated morphologic phenotypes of treated cells with immunofluorescence. The induction of apoptosis was evaluated using caspase-3/7 activation and TUNEL staining. Colony forming assays were used to test oncogenic transformation and xenograft studies with patient-derived cell lines were used to evaluate the effects of HCI2509 on tumorigenesis. Results: HCI2509 caused a dramatic reversal of both the up- and downregulated transcriptional profiles of EWS/FLI and EWS/ERG accompanied by the induction of apoptosis and disruption of morphologic and oncogenic phenotypes modulated by EWS/FLI. Importantly, HCI2509 displayed single-agent efficacy in multiple xenograft models. Conclusions: These data support epigenetic modulation with HCI2509 as a therapeutic strategy for Ewing sarcoma, and highlight a critical dual role for LSD1 in the oncogenic transcriptional activity of EWS/ETS proteins. Clin Cancer Res; 20(17); 4584–97. ©2014 AACR.
Standardized Reprocessing of Reusable Colonoscopy Biopsy Forceps is Effective: Results of a German Multicenter Study
Authors: M. Jung, U. Beilenhoff, M. Pietsch, B. Kraft, G. Rippin
Journal: Endoscopy (2003)

National and international guidelines recommend that a standardized protocol consisting of cleaning, ultrasound cleaning, and sterilization should be used for the reprocessing of endoscopic accessories in order to reduce the risk of transmission of microorganisms. This German multicenter study investigated the efficacy of standardized reprocessing of reusable biopsy forceps used during colonoscopy.Ten endoscopy centers (eight hospitals and two private practices) used 330 biopsy forceps during routine colonoscopy. The forceps were used once, five times, or 20 times for colonoscopy, based on a randomization plan. The reprocessing protocol consisted of manual cleaning with an enzymatic agent, ultrasound cleaning with an enzymatic agent (30 min, 40 degrees C, 47 Hz), neutralization, drying, and sterilization (5 min, 134 degrees C). Aldehydes were not used, and the protocol did not include a disinfection step. The biopsy forceps were sent to three microbiological institutes, based on a randomization plan, to have them tested for the presence of organisms, including identification of bacteria.A total of 318 of the 330 forceps were evaluable; 314 forceps (98.74 %) were sterile after use once, five times, or 20 times. Four forceps were contaminated with Staphylococcus epidermidis (n = 2), Bacillus licheniformis (n = 1) and Corynebacterium aquaticum (n = 2). All of 25 forceps were sterile after being used 20 times.Colonoscopy biopsy forceps can be reliably reprocessed following this standardized protocol, even without aldehydes.
Metabolism and Effects of Epidermal Growth Factor and Related Growth Factors in Mammals*
Authors: DELBERT A. FISHER, JAYARAMAN LAKSHMANAN
Journal: Endocrine Reviews (1990)

The initial observations of Stanley Cohen in the 1960s established that EGF induced in vivo effects such as precocious eyelid opening and tooth eruption. Subsequently the actions of EGF have been extensively explored in cell culture systems. The receptor for EGF was characterized as a prototype model for other growth factors and the now extensive in vitro data indicate multiple functions for EGF. Moreover, EGF and EGF receptors have been characterized in many tissues, and EGF has been identified in most body fluids of several mammalian species. Interestingly, neither EGF antibody administration to newborn animals nor passive immunization of pregnant rodents against EGF has caused major deleterious effects (except the delay in epidermal maturation events), as might be expected from the in vitro studies. This is in contrast to the effects of nerve growth factor antiserum in developing rodents. Also, to date, no pathological EGF deficiency disorder has been characterized. However, the EGF family of growth factors appears to be important in mammalian development and function, although the precise roles and significance are not yet clear. Members of the family may have a role in embryogenesis and fetal growth since receptors have been identified in fetal tissues. Available evidence suggests that TGF alpha subserves the growth factor family roles in fetal development. In the developing postnatal animal pro-EGF mRNA, immunoreactive EGF, immunoreactive TGF alpha, and EGF receptors are present in many tissues. EGF also is produced and secreted by the maternal mammary gland, and mammary derived EGF appears to be important in gut development in the neonatal rodent. There is now extensive data to indicate important hormone-EGF interactions. In the postnatal period, thyroid and steroid hormones including retinoic acid have been shown to modulate EGF and/or EGF receptors in several tissues. GH increases EGF binding in liver and increases urine EGF concentrations. Moreover, EGF stimulates secretion of several hypothalamic and pituitary hormones, increases placental production of hCG and human chorionic somatomammotropin, increases adrenal cortisol production, and inhibits testicular, ovarian, and thyroid hormone secretions. As summarized in this review EGF has been implicated in a number of developmental events including palate and skin differentiation, growth of hair follicles, eye opening and tooth eruption, lung maturation, gut and liver growth, and differentiation of neurons. These EGF actions probably are mediated via autocrine, paracrine, and endocrine routes. A role for salivary and urine EGF in the maintenance of adult stomal, gut, and urinary epithelial surface integrity seems likely, although not yet proven.(ABSTRACT TRUNCATED AT 400 WORDS)
EPIDIDYMO-ORCHITIS COMPLICATING TYPHOID FEVER.
Authors: CHARLES M. NICE
Journal: JAMA (1907)

The following case is reported because epididymo-orchitis is a comparatively rare complication in typhoid fever, being discussed by most writers as orchitis, occurring after convalescence has begun, and usually with a previous history of specific urethritis. This case is un-usual in its differences. <h3>History.</h3> —L. B., white, male, aged 25, book-keeper, was seen Sept. 28, 1907. The family history was negative. He was of good habits and did not use alcohol or tobacco. He had had the diseases of childhood but no serious illness. He positively denied a history of urethritis or other venereal disease. His present illness began with an attack of typhoid fever of mild type beginning six weeks previously. Temperature reached normal on twentieth day. Four days later, after indiscretion in diet, he suffered a relapse. This was uneventful with the exception of frequent attacks of marked pain over a greatly enlarged spleen until the nineteenth day of
Immune correlates of metastatic melanoma patients treated with ipilimumab in combination with fotemustine in the phase II NIBIT-M1 study
Authors: Cristina Maccalli, Hugues Nicolay, Filippo Capocefalo, Ester Fonsatti, Carla Chiarucci, Ornella Cutaia, Diana Giannarelli, Giorgio Parmiani, Anna Maria Di Giacomo, Michele Maio
Journal: Journal for ImmunoTherapy of Cancer (2013)

Meeting abstracts Ipilimumab (IPI) in combination with fotemustine (FTM) has shown a promising clinical activity in metastatic melanoma (MM) patients (pts) enrolled in the NIBIT-M1 trial (Di Giacomo, et al., Lancet Oncology, 2012). This study investigated changes in immunological parameters in the
Fluvoxamine-induced bullous eruption mimicking hand-foot syndrome and intertrigo-like eruption: Rare cutaneous presentations and elusive pathogenesis
Authors: Chiao-Li Ke, Cheng-Chung Chen, Chien-Te Lin, Gwo-Shing Chen, Chee-Yin Chai, Shih-Tsung Cheng
Journal: Journal of the American Academy of Dermatology (2006)
Paradoxical cAMP-Induced Lung Endothelial Hyperpermeability Revealed by <i>Pseudomonas aeruginosa</i> ExoY
Authors: Sarah L. Sayner, Dara W. Frank, Judy King, Hairu Chen, John VandeWaa, Troy Stevens
Journal: Circulation Research (2004)

Mammalian transmembrane adenylyl cyclases synthesize a restricted plasmalemmal cAMP pool that is intensely endothelial barrier protective. Bacteria have devised mechanisms of transferring eukaryotic factor-dependent adenylyl cyclases into mammalian cells. Pseudomonas aeruginosa ExoY is one such enzyme that catalyzes cytosolic cAMP synthesis, with unknown function. Pseudomonas aeruginosa genetically modified to introduce only the ExoY toxin elevated cAMP 800-fold in pulmonary microvascular endothelial cells over 4 hours, whereas a catalytically deficient (ExoY(K81M)) strain did not increase cAMP. ExoY-derived cAMP was localized to a cytosolic microdomain not regulated by phosphodiesterase activity. In contrast to the barrier-enhancing actions of plasmalemmal cAMP, the ExoY cytosolic cAMP pool induced endothelial gap formation and increased the filtration coefficient in the isolated perfused lung. These findings collectively illustrate a previously unrecognized mechanism of hyperpermeability induced by rises in cytosolic cAMP.
Serum Antiplasmin and Plasmin in Rheumatoid Arthritis
Authors: D.P. Page Thomas, J.T.M. Dingle
Journal: Annals of the Rheumatic Diseases (1955)

<h3>Abstract</h3> Retinal ganglion cells (RGCs), which relay visual information from the eye to the brain, are the first cell type generated during retinal neurogenesis. Loss of function of the transcription factor <i>Atoh7</i>, which is expressed in multipotent early neurogenic retinal progenitor cells, leads to a selective and near complete loss of RGCs. <i>Atoh7</i> has thus been considered essential for conferring competence on progenitors to generate RGCs. However, when apoptosis is inhibited in <i>Atoh7-</i>deficient mice by loss of function of <i>Bax</i>, only a modest reduction in RGC number is observed. Single-cell RNA-Seq of <i>Atoh7;Bax</i>-deficient retinas shows that RGC differentiation is delayed, but that RGC precursors are grossly normal. <i>Atoh7;Bax</i>-deficient RGCs eventually mature, fire action potentials, and incorporate into retinal circuitry, but exhibit severe axonal guidance defects. This study reveals an essential role for <i>Atoh7</i> in RGC survival, and demonstrates <i>Atoh7-</i>independent mechanisms for RGC specification.
Decades after recovery from hepatitis B and HBsAg clearance the CD8+ T cell response against HBV core is nearly undetectable
Authors: Helenie Kefalakes, Christoph Jochum, Gudrun Hilgard, Alisan Kahraman, Anna Margarethe Bohrer, Nicolai El Hindy, Falko Markus Heinemann, Jens Verheyen, Guido Gerken, Michael Roggendorf, Joerg Timm
Journal: Journal of Hepatology (2015)
A targeted adenovirus vector displaying a human fibronectin type III domain-based monobody in a fiber protein
Authors: Hayato Matsui, Fuminori Sakurai, Kazufumi Katayama, Yasuhiro Abe, Mitsuhiro Machitani, Shinnosuke Kurachi, Masashi Tachibana, Hiroyuki Mizuguchi
Journal: Biomaterials (2013)
Low-Dose Exposure and Immunogenicity of Transgenic Maize Expressing the <i>Escherichia coli</i> Heat-Labile Toxin B Subunit
Authors: April J. Beyer, Kan Wang, Amber N. Umble, Jeffrey D. Wolt, Joan E. Cunnick
Journal: Environmental Health Perspectives (2006)

Transgenic maize, which produces the nontoxic B subunit of the Escherichia coli heat-labile toxin (LT-B) in seed, has proven to be an effective oral immunogen in mice. Currently, there is considerable concern over accidental consumption of transgenic maize expressing LT-B by humans and domestic animals. We have yet to define nonimmunogenic levels of transgenic LT-B when ingested.Our goal in this study was to determine the highest dose of LT-B orally administered in mice that does not result in a measurable immune response. We defined an immune response as specific serum or mucosal IgG or IgA significantly greater than background after three feedings (0.0002-20 mug) or a priming response induced by the intermittent feeding.We fed transgenic maize pellets on days 0, 7, 21, and 49 and collected serum and fecal samples weekly. Serum was analyzed for LT-B-specific IgG and IgA, and feces was analyzed for LT-B-specific IgA.We observed a dose-dependent anti-LT-B antibody response with high specific antibody concentrations in groups fed high doses (0.2, 2, 20 mug) of LT-B maize. Mice fed 0.02 mug LT-B demonstrated immune priming in 62.5% of the animals. Mice that were fed </= 0.002 mug LT-B showed no increase in specific antibody nor did they demonstrate immune priming, indicating that 0.002 mug LT-B was the highest nonimmunogenic dose tested.Our results demonstrate that LT-B derived from transgenic maize is immunogenic at nanogram levels when orally administered to mice.
Teaching Geriatrics-Reply
Authors: Robert N. Butler
Journal: JAMA (1981)

<h3>In Reply.—</h3> I am sorry that Dr Portnoi misunderstands the intent of the teaching nursing home. I do not regard the "institutional setting (hospital and nursing home) as the most important site placements for teaching geriatrics to medical students and senior residents." I do regard it as essential that both ambulatory and institutional settings be available for teaching and research to advance our knowledge about the care of older patients.
Iron mobilization from ferritin by superoxide derived from stimulated polymorphonuclear leukocytes. Possible mechanism in inflammation diseases.
Authors: P Biemond, H G van Eijk, A J Swaak, J F Koster
Journal: Journal of Clinical Investigation (1984)

During inflammation, the superoxide anion (O-2) and hydrogen peroxide (H2O2) are produced by stimulated polymorphonuclear leukocytes and macrophages. The toxic effects of these reactive oxygen intermediates increase when traces of iron are present, because iron catalyzes the formation of the hydroxyl radical (OH.). Partially saturated iron-binding proteins, such as transferrin and ferritin, are unable to catalyze OH. formation in vitro. Mobilization of iron from these proteins is necessary for iron stimulation of OH. formation. This paper reports that stimulated polymorphonuclear leukocytes mobilize iron from human and horse ferritin, but not from human transferrin. Iron release from ferritin depends on O-2 because it can be prevented by the addition of superoxide dismutase. Catalase and dimethylsulfoxide have no inhibitory effect on iron mobilization. The efficiency of the iron release increases at low levels of O-2 production. Only O-2 produced by granulocytes is sufficient for iron mobilization, because solid potassium superoxide is also able to release iron from ferritin. We propose that this reaction may potentiate the formation of the OH. radical in inflammatory states.
Designing a vaccine for tuberculosis
Authors: A. S Malin, D. B Young
Journal: BMJ (1996)

Tuberculosis is a disease of superlatives. Mycobacterium tuberculosis causes more deaths annually than any other infectious agent.1 Globally, it is one of the major pathogens associated with HIV disease.1 The tuberculosis vaccine, BCG, has been given to more people than any other vaccine.2 3 However, although this vaccine confers clear benefit against disseminated childhood tuberculosis, its efficacy against adult pulmonary disease has varied widely in different clinical trials.2 4 Curiously, protection induced by BCG seems to improve with increasing distance from the equator.2 In a large randomised controlled trial in Madras, southern India, and a large observational study in Malawi, BCG was no better than saline.3 5 It would be good to do better.

The reasons for the failure of BCG in adults remain unclear. Indeed, immunity to tuberculosis is poorly understood both at a cellular and molecular level.1 6 It is possible that the ability of BCG to protect against initial infection may wane with time. Alternatively, BCG may …
Molecular mechanisms in nickel carcinogenesis: modeling Ni(II) binding site in histone H4.
Authors: Maria Antonietta Zoroddu, Laura Schinocca, Teresa Kowalik-Jankowska, Henryk Kozlowski, Konstantin Salnikow, Max Costa
Journal: Environmental Health Perspectives (2002)

Ni(II) compounds are well known as human carcinogens, though the molecular events which are responsible for this are not yet fully understood. It has been proposed that the binding of N(II) ions within the cell nucleus is a crucial element in the mechanism of carcinogenesis. The most abundant proteins in the cell nucleus are histones, and this makes them the prime candidates for this role. This article is a review of our recent studies of histone H4 models of Ni(II) binding. We analyzed the sequence of the N-terminal tail of the histone H4, Ac-SGRGKGGKGLGKGGAKRH(18)RKVL-Am, for Ni(II) binding. This site has been proposed mainly because of the potent inhibitory effect of Ni(II) on the acetylation of lysine residues near the histidine H(18), and also because of the accessibility of the H4 tail in the histone octamer. Combined potentiometric and spectroscopic studies showed that the histidine 18 acted as an anchoring binding site for metal ions in the peptide investigated. Comparison with the results for Cu(II) binding are also reported. The results allowed us to propose that the binding of Ni(II) is able to promote a secondary structure with organized side-chain orientation on the N-terminal tail of histone H4.
Preparation of Electrocardiographic Data for Analysis by Digital Electronic Computer
Authors: HUBERT V. PIPBERGER, EDWARD D. FREIS, LEONARD TABACK, HENRY L. MASON
Journal: Circulation (1960)

A pilot facility for automatic processing of electrocardiograms leading to their analysis by digital computer has been described. Wave forms from orthogonal electrocardiographic leads were recorded on magnetic tape. By means of newly designed conversion equipment these records have been converted from their original analog form into digital form. The further processing and analysis of the data thus becomes feasible through the use of commercially available digital electronic computers. It has been demonstrated that the electrocardiographic tracings as recorded from patients can be reproduced from the resulting numerical print-outs in their original and undistorted form. The further analysis of these records then requires only proper programming of a digital computer. The same equipment with minor modifications can be used for automatic processing of other analog data such as phonocardiograms, pulse tracings, and ballistocardiograms.
Hitler's Psychopathology
Authors: Jonathan M. Raines
Journal: JAMA (1985)

Numerous psychiatrists and historians have speculated about the nature of Hitler's personality and motivation. During World War II, the Office of Strategic Services, under the direction of psychoanalyst Walter C. Langer, prepared a dossier for American intelligence, which was ultimately declassified and published in 1972 as The Mind of Adolf Hitler. Hitler's  Psychopathology is, to my knowledge, the first comprehensive work to examine the voluminous historical record amassed since the preparation of the Office of Strategic Services study using the framework of current thought on the development and structure of personality.  In the introductory chapters, the authors offer their diagnosis: narcissistic personality with paranoid features functioning on a borderline personality level. In the succeeding three sections, the details of Hitler's personal and political life are compared with the diagnostic hypothesis.  Individuals with such disorders can be characterized by their use of certain defense mechanisms to deal with internal conflicts, the
Falsification of an Immunization Certificate
Authors: Henry M. Feder
Journal: JAMA (1992)

<h3>To the Editor.</h3> —A 6-year-old boy presented to the University of Connecticut Family Medicine office for well-child care. He had just arrived in the United States, having received al<sup>1</sup>prior care in Europe. The parents brought an immunization certificate that listed the following immunizations and dates: BCG vaccine (January 16, 1985); polio (February 27, 1985; May 31, 1985; November 27,1985); diphtheria-pertussis-tetanus (DPT) (April 24, 1985; May 31,1985; June 20,1985; December 26,1986; November 29, 1987); and measles (February 1, 1986). However, according to the parents, their child had only received one or two parenteral and oral immunizations because of a local vaccine shortage. The parents were not told what immunizations were given and had never seen their child's immunization records. The immunization certificate was filled out when the family was leaving Romania and the parents did not know how the information on the certificate was obtained. Because the validity of
SULPHANILAMIDE DETERMINATION IN SPONTANEOUS AND CANTHARIDIN BLISTERS IN VESICULAR AFFECTIONS OF THE SKIN (PEMPHIGUS, DERMATITIS HERPETIFORMIS, HERPES GESTATIONIS, EPIDERMOLYSIS BULLOSA HEREDITARIA)
Authors: A. DOSTROVSKY, F. SAGHER
Journal: British Journal of Dermatology (1945)
Drinking-Water Herbicide Exposure in Indiana and Prevalence of Small-for-Gestational-Age and Preterm Delivery
Authors: Hugo Ochoa-Acuña, Jane Frankenberger, Leighanne Hahn, Cristina Carbajo
Journal: Environmental Health Perspectives (2009)

Atrazine and other corn herbicides are routinely detected in drinking water. Two studies on potential association of atrazine with small-for-gestational-age (SGA) and preterm birth prevalence found inconsistent results. Moreover, these studies did not control for individual-level potential confounders.Our retrospective cohort study evaluated whether atrazine in drinking water is associated with increased prevalence of SGA and preterm birth.We developed atrazine concentration time series for 19 water systems in Indiana from 1993 to 2007 and selected all births (n = 24,154) based on geocoded mother's residences. Log-binomial models were used to estimate prevalence ratios (PRs) for SGA and preterm delivery in relation to atrazine concentrations during various periods of the pregnancy. Models controlled for maternal demographic characteristics, prenatal care and reproductive history, and behavioral risk factors (smoking, drinking, drug use).Atrazine in drinking water during the third trimester and the entire pregnancy was associated with a significant increase in the prevalence of SGA. Atrazine in drinking water > 0.1 microg/L during the third trimester resulted in a 17-19% increase in the prevalence of SGA compared with the control group (< 0.1 microg/L). Mean atrazine concentrations over the entire pregnancy > 0.644 microg/L were associated with higher SGA prevalence than in the control group (adjusted PR = 1.14; 95% confidence interval, 1.03-1.24). No significant association was found for preterm delivery.We found that atrazine, and perhaps other co-occurring herbicides in drinking water, is associated with an increased prevalence of SGA, but not preterm delivery.