tbuckley/cabot-search huggingface dataset:
Genome-Wide Analysis of Alternative Splicing in Medulloblastoma Identifies Splicing Patterns Characteristic of Normal Cerebellar Development
Authors: Francesca Menghi, Thomas S. Jacques, Martino Barenco, Ed C. Schwalbe, Steven C. Clifford, Mike Hubank, Jonathan Ham
Journal: Cancer Research (2011)

Alternative splicing is an important mechanism for the generation of protein diversity at a post-transcriptional level. Modifications in the splicing patterns of several genes have been shown to contribute to the malignant transformation of different tissue types. In this study, we used the Affymetrix Exon arrays to investigate patterns of differential splicing between pediatric medulloblastomas and normal cerebellum on a genome-wide scale. Of the 1,262 genes identified as potentially generating tumor-associated splice forms, we selected 14 examples of differential splicing of known cassette exons and successfully validated 11 of them by reverse transcriptase PCR. The pattern of differential splicing of three validated events was characteristic for the molecular subset of sonic hedgehog (Shh)-driven medulloblastomas, suggesting that their unique gene signature includes the expression of distinctive transcript variants. Generally, we observed that tumor and normal fetal cerebellar samples shared significantly lower exon inclusion rates than normal adult cerebellum. We investigated whether tumor-associated splice forms were expressed in primary cultures of Shh-dependent mouse cerebellar granule cell precursors (GCP) and found that Shh caused a decrease in the cassette exon inclusion rate of five of the seven tested genes. Furthermore, we observed a significant increase in exon inclusion between postnatal days 7 and 14 of mouse cerebellar development, at the time when GCPs mature into postmitotic neurons. We conclude that inappropriate splicing frequently occurs in human medulloblastomas and may be linked to the activation of developmental signaling pathways and a failure of cerebellar precursor cells to differentiate.
Degradation products of fibrinogen by elastase-like neutral protease from human granulocytes. Characterization and effects on blood coagulation in vitro.
Authors: M Gramse, C Bingenheimer, W Schmidt, R Egbring, K Havemann
Journal: Journal of Clinical Investigation (1978)

We investigated the effect of elastase-like neutral protease isolated from human granolocytes on human fibrinogen. Dependent on enzyme concentration and time of incubation, the elastase-like protease induced a progressive degradation of fibrinogen. Analysis of the remaining polypeptide chains showed a high susceptibility of the Aalpha- and low susceptibility of the gamma-chain of fibrinogen towards the proteolytic action of the enzyme. The split products were characterized by polyacrylamide gel electrophoresis and two-dimensional immunoelectrophoresis. They showed antigenic determinants of fibrinogen and of plasmin-induced proteolysis products D and E. The cleavage fragments isolated by gel chromatography had distinct molecular weights. Coagulability of fibrinogen by thrombin was inhibited according to the concentration of the protease and the time of incubation. Split products of fibrinogen with higher molecular weight prolonged the coagulation time of native fibrinogen, whereas low molecular weight fragments were ineffective.
Characterization of a human lymphocyte surface sialoglycoprotein that is defective in Wiskott-Aldrich syndrome.
Authors: E Remold-O'Donnell, D M Kenney, R Parkman, L Cairns, B Savage, F S Rosen
Journal: The Journal of Experimental Medicine (1984)

gpL115 is a lymphocyte surface component that is deficient in patients with the X-chromosome-linked immune deficiency Wiskott-Aldrich syndrome (6). The glycoprotein nature of gpL115 is demonstrated through labeling in carbohydrate moieties by [3H]NaBH4 and its synthesis by lymphocytes through labeling with [35S]methionine. Native gpL115 adheres to wheat germ lectin-Sepharose and sialidase-treated gpL115 does not adhere, indicating that native gpL115 adheres via clusters of sialic acid residues. When tested on peanut lectin, which shows specificity for the disaccharide Gal beta 1-3GalNAc, gpL115 is nonadherent and sialidase-treated gpL115 is adherent, indicating the presence of the sequence sialic acid-Gal beta 1-3GalNAc, which is characteristic for O-linked (mucin-type, acidic-type) carbohydrates. A surface glycoprotein with all the above characteristics was found on the lymphoblastoid cell line CEM. CEM cells were used as immunogen to generate the monoclonal antibody L10, an IgG1, which binds native and sialidase-treated gpL115 . Sialidase-treatment of gpL115 significantly alters its physical properties, reducing its electrophoretic mobility and changing its behavior on isoelectrofocusing. Cumulatively, these findings indicate that gpL115 , like glycophorin of erythrocytes and GPIb of platelets, is a sialoglyco protein with significant quantities of O-linked carbohydrate. On treatment with limiting sialidase concentrations, gpL115 of normal lymphocytes is transformed into a series of partially desialylated species of decreasing electrophoretic mobility. This finding resembles the situation with lymphocytes of some Wiskott-Aldrich syndrome patients. Lymphocytes of eight Wiskott-Aldrich syndrome patients were found to be deficient in 125I-labeled gpL115 . Lymphocytes from three of these patients displayed an abnormal 125I-component of apparent mol wt 135,000.
Trouble comes in twos
Authors: Anna Goodman
Journal: BMJ (2005)

in tissue structure and function that counterbalance its effects-so called canalisation. 7 Conclusion8][19][20] Importantly, the inferences are concerned with attribution of causality that is relevant to whole populations and are not concerned with targeting interventions on those with specific genetic variants.By applying the increasing knowledge of human genetics, it is possible to improve knowledge of how diverse environmental exposures, many of which are socially patterned, shape population health and where future public health prevention should be targeted.We thank Nancy Krieger, John Lynch, and Neil Pearce for their comments.Contributors and sources: GDS and SE are experienced epidemiologists
Coffee Intake and Serum Lipids in Men
Authors: Philip I. Hershberg
Journal: JAMA (1985)

<h3>To the Editor.—</h3> Williams et al<sup>1</sup>note that male heavy coffee drinkers have lipoprotein profiles suggestive of increased cardiovascular risk. Other studies, at least in Americans, are noted to be nonsupportive. From 1970 to 1972, an unpublished study was performed under National Aeronautics and Space Administration sponsorship in 918 cardiac patients and in 918 age- and sex-matched controls, both groups consisting of patients of the Lahey Clinic Foundation. These patients were drawn from over 90,000 who had completed a detailed questionnaire that included the question, how many cups of coffee do you drink each day? The answers were as follows: none, 281; less than one, 282; one to three, 283; four to six, 284; and more than six, 285. Although we did not consider the influences of confounding factors, we believe that the sample considered, over 23 times greater than that in the published report by Williams et al,
Efficacy of Holter Monitors
Authors: David A. Lantz
Journal: Annals of Internal Medicine (1996)

Letters15 October 1996Efficacy of Holter MonitorsDavid A. Lantz, MDDavid A. Lantz, MD74th Medical Group, Wright Patterson Air Force Base, OH 45433Author, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-125-8-199610150-00021 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail TO THE EDITOR:It was with great interest that we read the recent report of the study in which Kinlay and colleagues prospectively compared Holter monitors with cardiac event recorders for assessment of intermittent palpitations [1]. The authors concluded that event recorders provide better data and are more cost-effective. We previously reviewed and presented data [2] on the utility of Holter monitoring at our institution.We reviewed 278 consecutive Holter recordings for demographic data, reason for study, presence of significant dysrhythmias (atrial fibrillation, paroxysmal superventricular tachycardia, ventricular tachycardia, significant pauses, and atrioventricular block), symptom correlation, and source of referral. We ...References1. Kinlay S, Leitch JW, Neil A, Chapman BL, Hordy DB, Fletcher BJ. Cardiac event recorders yield more diagnoses and are more cost-effective than 48-hour Holter monitoring in patients with palpitations. A controlled clinical trial. Ann Intern Med. 1996; 124:16-20. Google Scholar2. Maher W, Chang G, Lantz D. Is the Holter monitor at David Grant Medical Center a useful test? Proceedings of the Society of Air Force Physicians Regional ACP Meeting. St. Louis; 1993. Google Scholar Author, Article, and Disclosure InformationAuthors: David A. Lantz, MDAffiliations: 74th Medical Group, Wright Patterson Air Force Base, OH 45433Disclaimer: The opinions expressed are solely those of the author and not the Department of Defense. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited byClinical Logistics in 24-Hour Ambulatory Electrocardiographic Monitoring 15 October 1996Volume 125, Issue 8Page: 697-698KeywordsCardiovascular therapyElectrophysiological techniquesInformation storage and retrievalIschemiaLongitudinal studiesOutpatientsPatientsSyncopeTachycardiaVentricular tachycardia ePublished: 15 August 2000 Issue Published: 15 October 1996 Copyright & PermissionsCopyright © 1996 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
Role of a major autoepitope in forming the DNA binding site of the p70 (Ku) antigen.
Authors: C H Chou, J Wang, M W Knuth, W H Reeves
Journal: The Journal of Experimental Medicine (1992)

The Ku antigen is a heterodimer consisting of 70- and 80-kD protein subunits that binds to termini of double-stranded DNA. DNA binding appears to be mediated partly by the 70-kD (p70) subunit, but the precise mechanism of its association with DNA is unclear. High-titer autoantibodies in sera from certain patients with systemic lupus erythematosus recognize at least eight distinct epitopes of Ku, and inhibit DNA binding. In the present studies, the binding of DNA to truncated p70 fusion proteins was determined in Southwestern blots and DNA immunoprecipitation assays. Appropriate folding of the p70 protein was crucial for efficient DNA binding. The minimal DNA binding site, amino acids 536-609, contains a major conformational autoepitope of p70 (amino acids 560-609). Deletion of amino acids 601-609, or substitution of ala-ala-ala for lys-ser-gly at positions 591-593, eliminated DNA binding as well as autoantibody binding, suggesting that the same secondary or supersecondary structure is involved in both DNA binding and autoantibody recognition. Residues within the DNA binding site/autoepitope closely resemble the helix-turn-helix motif in bacteriophage lambda Cro protein and certain other DNA binding proteins, and mutations predicted to destabilize this structure eliminated DNA binding. Adjacent to the helix-turn-helix is a highly basic domain (positions 539-559) that was also required for DNA binding. The findings suggest that the DNA binding site of p70 consists of a basic domain adjacent to a helix-turn-helix structure that also forms a major autoepitope.
Relevance in Medical Education
Authors: Robert C. Wallach
Journal: JAMA (1970)

To the Editor:—  I read with interest, but dismay, the recent editorial on Relevance in Medical Education (212:314, 1970). Dr. Kent seems to suggest that medical students no longer be required to retain a mass of data including anatomy, physiology, pathology, immunology and so forth. He is not concerned about the students  to memorize and retrieve factual or conceptual information. He would not have the medical school test the students ability in these areas. He suggests that when the student knows the scientific method and where the sources of information are that the student will then be an adequate physician.  I certainly hope that when my family or I need medical care, there is a reactionary irrelevant physician available who is well versed in both the basic sciences and clinical applications and can make judgments on the basis of information that he has previously assimilated and worked with,
PRELIMINARY ACCOUNT OF AN INVESTIGATION OF FACTORS INFLUENCING LONGEVITY
Authors: RAYMON D PEARL
Journal: JAMA (1924)

Since its establishment, a major part of the research activities of the Department of Biometry and Vital Statistics of the School of Hygiene has been devoted to the study of life duration as a general biologic problem. We have attacked and are now working at this problem in a variety of ways, experimental, statistical, pathologic, historic and others.<sup>1</sup>As time goes on, the results of these various lines of inquiry will be published. The present paper is designed to show something of the potential significance and promise of what is, in some of its aspects at least, a novel method of approaching the general problem. It will be followed, unless something quite unforeseen prevents the accomplishment of the task, by detailed and definitive reports as the work progresses. The problem of life duration is one of great practical as well as theoretical importance. Normal human beings are directly and
Choledochocele, an Overlooked Diagnosis: Report of 15 Cases and Review of 56 Published Reports from 1984 to 1992
Authors: S. D. Ladas, I. Katsogridakis, P. Tassios, T. Tastemiroglou, T. Vrachliotis, S. A. Raptis
Journal: Endoscopy (1995)

Backround and Study Aims: Choledochocele (CDCL) is still regarded as being a rare abnormality, despite the increasing number of case reports published in the last ten years. The aim of this prospective study was to investigate the prevalence rate of CDCL in patients referred for endoscopic retrograde cholangiopancreatography (ERCP), as well as the short-term and long-term complications of endoscopic treatment.
711-4 Low Plasma Homocysteine Levels Predict Reduced Atheroma Burden in Patients Undergoing Coronary Interventions: Evidence from Intravascular Ultrasound
Authors: Ellen L. Mayer, Killian Robinson, Donald W. Jacobsen, E. Murat Tuzcu, Anthony C. De Franco, David J. Moliterno, Skip Guyer, Steven E. Nissen
Journal: Journal of the American College of Cardiology (1995)
Bullous pyoderma gangrenosum and multiple myeloma
Authors: J.J. HORTON, J.R. TROUNCE, D.M. MACDONALD
Journal: British Journal of Dermatology (1984)

Journal Article Bullous pyoderma gangrenosum and multiple myeloma Get access J.J. HORTON, J.J. HORTON Departments of Dermatology, Guy's Hospital, London SE1, U.K. Search for other works by this author on: Oxford Academic Google Scholar J.R. TROUNCE, J.R. TROUNCE Clinical Pharmacology, Guy's Hospital, London SE1, U.K. Search for other works by this author on: Oxford Academic Google Scholar D.M. MACDONALD D.M. MACDONALD Departments of Dermatology, Guy's Hospital, London SE1, U.K. Dr D.M.MacDonald, Department of Dermatology, Guy's Hospital, St Thomas' Street, London SE1 9RT, U.K. Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 111, Issue 2, 1 August 1984, Pages 227–230, https://doi.org/10.1111/j.1365-2133.1984.tb04048.x Published: 01 August 1984 Article history Accepted: 07 February 1984 Published: 01 August 1984
Decreased Spinal Mineral Content in Amenorrheic Women
Authors: Christopher E. Cann
Journal: JAMA (1984)

Premenopausal amenorrheic women may be at risk for the development of osteoporosis. In hyperprolactinemia, cortical bone mass is decreased and the magnitude of the decrease correlates with the severity of the estrogen deficiency. However, bone loss in women with amenorrhea from other causes has not been assessed. We have studied women with hypothalamic and hyperprolactinemic amenorrhea and premature ovarian failure. Bone mass in the peripheral cortical bone was only slightly decreased from age-matched controls, but spinal trabecular bone was decreased 20% to 30%. Estradiol levels were 20 to 80 pg/mL in these women, not different from normal early follicular levels. The decrease in bone mass in the spine did not correlate with serum estradiol at these levels. The hypothalamic amenorrhea group was made up of athletes in whom the bone mass decrease was an unexpected finding.
Monocytosis in Malignant Disease
Authors: O'NEILL BARRETT
Journal: Annals of Internal Medicine (1970)

The absolute monocyte count was determined in 100 normal individuals and in 100 patients with a variety of solid tumor malignancies. A significant elevation in the mean value for the latter group was found. Monocytosis is therefore of descriptive and diagnostic value in the evaluation of patients with solid tumor malignancy.
Characterization of the Chronic Risk and Hazard of Hazardous Air Pollutants in the United States Using Ambient Monitoring Data
Authors: Michael C. McCarthy, Theresa E. O’Brien, Jessica G. Charrier, Hilary R. Hafner
Journal: Environmental Health Perspectives (2009)

Ambient measurements of hazardous air pollutants (air toxics) have been used to validate model-predicted concentrations of air toxics but have not been used to perform risk screening at the national level.We used ambient concentrations of routinely measured air toxics to determine the relative importance of individual air toxics for chronic cancer and noncancer exposures.We compiled 3-year averages for ambient measurement of air toxics collected at monitoring locations in the United States from 2003 through 2005. We then used national distributions of risk-weighted concentrations to identify the air toxics of most concern.Concentrations of benzene, carbon tetrachloride, arsenic, 1,3-butadiene, and acetaldehyde were above the 10(-6) cancer risk level at most sites nationally with a high degree of confidence. Concentrations of tetrachloroethylene, ethylene oxide, acrylonitrile, and 1,4-dichlorobenzene were also often greater than the 10(-6) cancer risk level, but we have less confidence in the estimated risk associated with these pollutants. Formaldehyde and chromium VI concentrations were either above or below the 10(-6) cancer risk level, depending on the choice of agency-recommended 10(-6) level. The method detection limits of eight additional pollutants were too high to rule out that concentrations were above the 10(-6) cancer risk level. Concentrations of 52 compounds compared with chronic noncancer benchmarks indicated that only acrolein concentrations were greater than the noncancer reference concentration at most monitoring sites.Most pollutants with national site-level averages greater than health benchmarks were also pollutants of concern identified in modeled national-scale risk assessments. Current monitoring networks need more sensitive ambient measurement techniques to better characterize the air toxics problem in the United States.
Results of the Stent-Protected Angioplasty versus Carotid Endarterectomy (SPACE) study to treat symptomatic stenoses at 2 years: a multinational, prospective, randomised trial
Authors: Hans-Henning Eckstein, Peter Ringleb, Jens-Rainer Allenberg, Jürgen Berger, Gustav Fraedrich, Werner Hacke, Michael Hennerici, Robert Stingele, Jens Fiehler, Hermann Zeumer, Olav Jansen
Journal: The Lancet Neurology (2008)
A role for a new vascular enzyme in the metabolism of xenobiotic amines.
Authors: P J Boor, R M Hysmith, R Sanduja
Journal: Circulation Research (1990)

Although it has long been thought that environmental toxins may play an underlying role in vascular diseases such as atherosclerosis, this concept is not supported by any clear-cut experimental evidence of toxic metabolism by cardiovascular enzymes. In this study, we demonstrate that allylamine, a selective cardiovascular toxin in vivo, is actively metabolized in vitro by a purified vascular enzyme (semicarbazide-sensitive amine oxidase), which has been localized recently to vascular smooth muscle cells. Oxidative deamination of allylamine to a highly toxic aldehyde, acrolein, was blocked through enzyme inhibition by semicarbazide-sensitive amine oxidase suggests that this vascular enzyme's physiological role may include metabolism of exogenous amines.
ELECTRON MICROSCOPIC OESERVATIONS ON THE LESIONS OF CONDYLOMA LATUM
Authors: TERUHIKO HASEGAWA
Journal: British Journal of Dermatology (1969)

SUMMARY. Biopsy specimens of the lesions of condyloma latum were examined by electron microscopy. Spirochaetes were found in the dermis, but not in plasma cells. These spirochaetes were almost identical in structure to Nichols virulent spirochaetes. The plasma cells had a strongly developed endoplasmic reticulum, and in some of them expansion of the endoplasmic reticulum and dilatation of the Golgi area were noted.
OT3-02-02: Yoga Compared to Exercise as a Therapeutic Intervention during (Neo)adjuvant Chemotherapy in Women with Stage I-III Breast Cancer.
Authors: F Wiedemann, A Büssing, M Halle, M Kiechle, N Kohls, T Ostermann, D Sattler, J Ettl
Journal: Cancer Research (2011)

Abstract Background: Psychological and physical distress is high in breast cancer patients receiving neoadjuvant or adjuvant chemotherapy. The ***patients'ability to cope with this distress has an impact on treatment variables, i.e. deliverable chemotherapy dose, tolerabilty of side effects, and finaly treatment completion rate. Exercise intervention studies have shown physiological and psychological benefits when undertaken during cancer treatment. There is also evidence that mind/body interventions such as yoga are useful to manage treatment-related symptoms and anxiety in breast cancer patients. Considering the specific theoretical background of mind/body interventions this ongoing trial aims to elucidate the different effects of yoga and conventional exercise on physical and psychological factors in breast cancer patients undergoing neoadjuvant or adjuvant chemotherapy. Trial design: Longitudinal data collection within an open, prospective, randomized trial using standardized questionnaires about inner correspondence and peacefulness with practices (ICPH), health-related quality of life (EORTC QLC C-30), fatigue (Cancer Fatigue Scale, CFS-D), mindfulness (Freiburg Mindfulness Inventory, FMI), spiritual/religious attitudes and disease coping (SpREUK), and life satisfaction (Brief Multidimensional Life Satisfaction Scale, BMLSS). Patients with newly diagnosed stage I-III breast cancer undergoing neoadjuvant or adjuvant chemotherapy are randomly assigned to receive yoga or conventional exercise on a 1:1 ratio. The yoga intervention consists of a weekly 60-minute Iyengar-Yoga group-session together with individual home-based, selfcontained 20-minute sessions twice a week. The conventional exercise intervention consists of a weekly 60-minute physiotherapy exercise session together with individual home-based, selfcontained 20-minute sessions twice a week. Data assessments via questionnaires are done at baseline, right after the 12-week intervention period and 2 months after the end of intervention. Statistical analysis includes analysis of variance with all collected parameters and analysis of correlation between ICPH and above parameters. For statistical power 1-β=0.8 and twosided probability of error a=0.05 the target accrual is 120 patients. Patient accrual within two breast care units started in April 2011 with 12 patients being on study to date (2011, June 21). Planned period of accrual is 20 months. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr OT3-02-02.