tbuckley/cabot-search huggingface dataset:
Abstract IA18: Activities of wild-type and mutant p53
Authors: Karen H. Vousden
Journal: Cancer Research (2013)

Abstract The p53 tumor suppressor protein restrains malignant progression through a number of mechanisms, and most cancers show loss of the normal functions of p53. In many cancers this is due to mutations in the p53 gene, leading to the expression of mutant p53 proteins that have lost wild type activity and acquired an oncogenic function that can promote metastasis. We have found that mutant p53 can promote the activation of integrin and cell surface receptor trafficking that depends on Rab-coupling protein (RCP) and which results in constitutive activation of signaling though the EGFR, MET and integrin. Simultaneous loss of p53 and p63 recapitulates the phenotype of mutant p53 both in cells and in vivo, and this function of mutant p53 reflects, at least in part, the inhibition of the p53 family member p63 . Interestingly, the tumor-associated point mutations induce conformational instability of the p53 protein, and the misfolding of p53 correlates with loss of wild type and gain of mutant activity. We have found that folding of wild type p53 is promoted by an interaction with the chaperonin CCT. Intriguingly, p53 proteins mutated to prevent the interaction with CCT show conformational instability, and acquire an ability to promote invasion and random motility that is similar to the activity of tumor derived p53 mutants. Our data therefore suggest that both growth suppression and cell invasion may be differentially regulated functions of wild type p53. Citation Format: Karen H. Vousden. Activities of wild-type and mutant p53. [abstract]. In: Proceedings of the Third AACR International Conference on Frontiers in Basic Cancer Research; Sep 18-22, 2013; National Harbor, MD. Philadelphia (PA): AACR; Cancer Res 2013;73(19 Suppl):Abstract nr IA18.
Spontaneous pneumomediastinum in adult dermatomyositis.
Authors: J D Bradley
Journal: Annals of the Rheumatic Diseases (1986)

Spontaneous pneumomediastinum has not been reported in adult polymyositis or dermatomyositis, either in conjunction with spontaneous pneumothorax or in isolation. Spontaneous pneumothorax has been rarely reported as a complication of rheumatoid arthritis, systemic lupus erythematosus, scleroderma, and childhood dermatomyositis. It is associated with active, progressive pulmonary involvement and a poor prognosis. We describe an adult with dermatomyositis and spontaneous pneumomediastinum with a favourable outcome.
Denileukin diftitox in combination with rituximab for previously untreated follicular B-cell non-Hodgkin's lymphoma
Authors: S M Ansell, H Tang, P J Kurtin, P A Koenig, G S Nowakowski, D A Nikcevich, G D Nelson, Z Yang, D M Grote, S C Ziesmer, P T Silberstein, C Erlichman, T E Witzig
Journal: Leukemia (2011)
Problems in the Staging of Hodgkin Disease
Authors: Robert H. Kirschner
Journal: JAMA (1973)

<h3>To the Editor.—</h3> We wish to comment on the article, "The Staging of Hodgkin's Disease: Selective vs Routine Laparotomy" (224:1026, 1973). Several points require discussion: The selection of which lymph nodes to biopsy is important. In addition to those listed by the authors, the largest porta hepatic lymph node should be chosen. These nodes are not reliably visualized by lymphangiography, may lie outside the usual radiation ports, and are the nodes most often involved when only solitary abdominal nodal disease is present.<sup>1</sup> Failure to discover occult abdominal disease in patients clinically stage I or II may be due to failure to biopsy nodes appearing abnormal on lymphangiography as proved by postoperative roentgenograms documenting their removal. In our experience the gross appearance of nodes at the operating table has not been reliable in predicting involvement by Hodgkin disease. Sectioning the spleen at 1-cm intervals has proved
Handwriting of the Insane.
Authors: Rufus C. Hartranft
Journal: JAMA (1895)

Philadelphia, Pa., April 18, 1895. <h3>To the Medical Profession:</h3> —With a view to especially important scientific results, I am studying the handwriting of the insane; and request your aid by way of the loan of documents, letters or written memoranda, or information having bearing upon the subject. My especial desire is to obtain a given form of letter from ten persons, suffering from different degrees of insanity, such as melancholia, hallucination, paresis, etc., any and all writing that will be of interest in the investigation. In return for your kindness and help, I will forward to you, free of charge, a full and complete report, together with drawings, diagrams, etc., embracing a full description of my work, which will be of use, help and value to not only the medical fraternity, but to humanity in general. Please note on each specimen of writing, the duration of the malady or disorder,
Central Role of High Density Lipoprotein in Plasma Free Cholesterol Metabolism
Authors: Charles C. Schwartz, Z. Reno Vlahcevic, Mones Berman, John G. Meadows, Richard M. Nisman, Leon Swell
Journal: Journal of Clinical Investigation (1982)

This study was designed to provide direct information on the in vivo metabolism in man of free (unesterified) cholesterol in the major lipoprotein classes. Five human subjects were administered one or two (simultaneous) of the following; [2-(14)C] mevalonic acid, high density lipoprotein (HDL)-free [(14)C] cholesterol, low density lipoprotein (LDL)-free [(14)C] cholesterol, and very low density lipoprotein (VLDL)-free [(3)H]cholesterol. Blood was then obtained at frequent intervals for at least 9 h, and the alpha(HDL) and beta(LDL + VLDL) lipoproteins were quickly separated by heparin-manganese precipitation to prevent ex vivo exchange of free cholesterol. After the administration of [(14)C]mevalonic acid the specific activity (disintegrations per minute/micromole) of free cholesterol in the alpha- and beta-lipoproteins increased for 3 h. During this period the alpha-free cholesterol specific activity was higher than the beta specific activity. After administration of VLDL and LDL labeled with free cholesterol, the alpha-free cholesterol specific activity reached a peak value within 20 min, at which time it was considerably lower than the beta-free cholesterol specific activity. When HDL labeled with free cholesterol was administered, a precursor product relationship was observed between the alpha-free cholesterol (precursor) and beta-free cholesterol (product) specific activities.A multicompartmental model was developed that contained the simplest structure necessary to fit all of the data obtained. The kinetic analysis revealed the presence of extensive exchange (20-85 mumol/min) of free cholesterol between HDL and a tissue pool(s) enriched with newly synthesized free cholesterol. It was found that virtually all (>95%) of the free cholesterol in the beta-lipoproteins (LDL+VLDL) cycles directly through HDL. The free cholesterol in LDL appears to behave in the same fashion as the free cholesterol in VLDL. The results show that there are marked differences in the kinetic behavior of the free cholesterol fractions of alpha- and beta-lipoproteins. There is extensive recycling of free cholesterol between HDL and tissue pools, and between HDL and the beta-lipoproteins; this recycling has been quantitated. The findings support the view that in vivo, the free cholesterol in HDL plays a central role in exchange reactions and in the vascular-tissue cholesterol transport system.
Private Eye weighs in against tobacco industry's attack on plain packaging
Authors: Z. Kmietowicz
Journal: BMJ (2013)

The satirical magazine Private Eye couldn’t resist sending up Japan Tobacco International’s efforts to derail the UK government’s plan to reduce the take-up of smoking among young people by introducing plain packaging. 

The antismoking group Ash has complained to the Advertising Standards Authority about an advertisement from JTI (the trading name for Gallagher) that has appeared …
Correlation of Vectorcardiogram and Electrocardiogram with Coronary Arteriogram
Authors: GERALD B. LEE, WILLIAM J. WILSON, KURT AMPLATZ, NAIP TUNA
Journal: Circulation (1968)

One hundred patients with suspected coronary heart disease were studied by vectorcardiography (VCG), electrocardiography (ECG), and coronary arteriography. Twenty-eight patients had VCG evidence of anterior infarction; 26 of this group had severe narrowing or obstruction of the left anterior descending branch. Five did not have anterior infarction by ECG. Twenty-seven patients had VCG evidence of diaphragmatic infarction; 25 of this group had severe narrowing of the right coronary artery or the left circumflex branch or both. Six of the 27 did not have ECG evidence of diaphragmatic infarction. Twelve patients had VCG evidence of posterior infarction whereas it was detected by ECG in only two. Only six of the 12, however, had severe narrowing of the nutrient arteries to the posterobasal part of the myocardium. Thirteen patients with infarction had severe narrowing but not total obstruction of a coronary artery. On the other hand, 15 patients had total obstruction of a major coronary vessel without actual infarction.
Case 6-1983
Authors: Richard C. Cabot, Robert E. Scully, Eugene J. Mark, Betty U. McNeely, John Shillito, Edward P. Richardson
Journal: New England Journal of Medicine (1983)

Presentation of CaseA 52-year-old man was admitted to the hospital because of seizures.The patient was a right-handed truck driver who was well until one year earlier, when he was said to have "bronchitis." Prednisone, 10 mg daily, and theophylline were prescribed. A dental extraction was performed at an unknown interval before entry. One month before admission he began to have frequent severe generalized headaches, which were accompanied by depression ascribed to the recent loss of his job. Anorexia developed, and he lost 5.5 kg in weight. On the day of entry he was noted to have almost continuous . . .
Adverse drug reactions as cause of admission to hospital: prospective analysis of 18 820 patients
Authors: Munir Pirmohamed, Sally James, Shaun Meakin, Chris Green, Andrew K Scott, Thomas J Walley, Keith Farrar, B Kevin Park, Alasdair M Breckenridge
Journal: BMJ (2004)

<h3>Abstract</h3> <b>Objective</b> To ascertain the current burden of adverse drug reactions (ADRs) through a prospective analysis of all admissions to hospital. <b>Design</b> Prospective observational study. <b>Setting</b> Two large general hospitals in Merseyside, England. <b>Participants</b> 18 820 patients aged &gt; 16 years admitted over six months and assessed for cause of admission. <b>Main outcome measures</b> Prevalence of admissions due to an ADR, length of stay, avoidability, and outcome. <b>Results</b> There were 1225 admissions related to an ADR, giving a prevalence of 6.5%, with the ADR directly leading to the admission in 80% of cases. The median bed stay was eight days, accounting for 4% of the hospital bed capacity. The projected annual cost of such admissions to the NHS is £466m (€706m, $847m). The overall fatality was 0.15%. Most reactions were either definitely or possibly avoidable. Drugs most commonly implicated in causing these admissions included low dose aspirin, diuretics, warfarin, and non-steroidal anti-inflammatory drugs other than aspirin, the most common reaction being gastrointestinal bleeding. <b>Conclusion</b> The burden of ADRs on the NHS is high, accounting for considerable morbidity, mortality, and extra costs. Although many of the implicated drugs have proved benefit, measures need to be put into place to reduce the burden of ADRs and thereby further improve the benefit:harm ratio of the drugs.
p90 ribosomal S6 kinase 2 promotes invasion and metastasis of human head and neck squamous cell carcinoma cells
Authors: Sumin Kang, Shannon Elf, Katherine Lythgoe, Taro Hitosugi, Jack Taunton, Wei Zhou, Li Xiong, Dongsheng Wang, Susan Muller, Songqing Fan, Shi-Yong Sun, Adam I. Marcus, Ting-Lei Gu, Roberto D. Polakiewicz, Zhuo (Georgia) Chen, Fadlo R. Khuri, Dong M. Shin, Jing Chen
Journal: Journal of Clinical Investigation (2010)

Head and neck squamous cell carcinoma (HNSCC) is one of the most common types of human cancer and frequently metastasizes to LNs. Identifying metastasis-promoting factors is of immense clinical interest, as the prognosis for patients with even a single unilateral LN metastasis is extremely poor. Here, we report that p90 ribosomal S6 kinase 2 (RSK2) promotes human HNSCC cell invasion and metastasis. We determined that RSK2 was overexpressed and activated in highly invasive HNSCC cell lines compared with poorly invasive cell lines. Expression of RSK2 also correlated with metastatic progression in patients with HNSCC. Ectopic expression of RSK2 substantially enhanced the invasive capacity of HNSCC cells, while inhibition of RSK2 activity led to marked attenuation of invasion in vitro. Additionally, shRNA knockdown of RSK2 substantially reduced the invasive and metastatic potential of HNSCC cells in vitro and in vivo in a xenograft mouse model, respectively. Mechanistically, we determined that cAMP-responsive element-binding protein (CREB) and Hsp27 are phosphorylated and activated by RSK2 and are important for the RSK2-mediated invasive ability of HNSCC cells. Our findings suggest that RSK2 is involved in the prometastatic programming of HNSCC cells, through phosphorylation of proteins in a putative signaling network. Moreover, targeting RSK2 markedly attenuates in vitro invasion and in vivo metastasis of HNSCC cells, suggesting that RSK2 may represent a therapeutic target in the treatment of metastatic HNSCC.
Glutamate receptor dynamics organizing synapse formation in vivo
Authors: Tobias M Rasse, Wernher Fouquet, Andreas Schmid, Robert J Kittel, Sara Mertel, Carola B Sigrist, Manuela Schmidt, Asja Guzman, Carlos Merino, Gang Qin, Christine Quentin, Frank F Madeo, Manfred Heckmann, Stephan J Sigrist
Journal: Nature Neuroscience (2005)
Task force recommends CT lung cancer screening for high risk smokers and ex-smokers
Authors: M. McCarthy
Journal: BMJ (2014)

Smokers and former smokers aged 55-80 who have a smoking history of 30 pack-years or more, and who are currently smoking or have quit within the past 15 years, should be screened annually with low dose computed tomography, the US Preventive Services Task Force has concluded.1

The panel recommended that screening should be discontinued once a person has not smoked for 15 years or has developed a health condition that limits the person’s life expectancy “or the ability or willingness to have curative lung surgery.”

The panel’s recommendations were published 31 December 2013 by the Annals of Internal Medicine .

Task force panels are charged with assessing the effectiveness of preventive care services for patients who do not have signs or symptoms of the screened condition. In drawing up their recommendations, panels weigh the benefits and harms of the intervention but do not consider …
Handbook of Pediatrics.
Authors: Herman F. Meyer
Journal: JAMA (1963)

This reviewer confesses that when he sought information from one of these "concentrates of knowledge," he had the same furtive guilt feeling as when he consulted a "pony" in translating Caesar. However, after living for several weeks with this handbook, he is amazed at the plethora of accurate data available at one's finger tips. A handbook within a specialty may be an excellent adjunct and time saver. The book is not an orientation in pediatrics, nor should it be considered other than a quick and accurate reference source for the details provided by this little "companion." It is most valuable to the experienced clinician who has perspective on the field in question and would lean on this source book for those fleeting facts which are beyond the possibility of storing within the recesses of memory. The publication of five editions since 1955, and translation into five languages, indicates the book's
It's an Insurance Problem, Not a Liability Crisis
Authors: Eugene I. Pavalon
Journal: JAMA (1987)

<h3>To the Editor.—</h3> I am responding to the summary of results from the latest survey of public opinion recently published by the American Medical Association (AMA).<sup>1</sup>It was not surprising to learn that the AMA survey of the public showed that "substantial majorities [of the public] are now sympathetic with positions [of the AMA] on a number of specific issues related to malpractice insurance and suits." The survey demonstrates that public opinion has been influenced by the multimillion-dollar media campaign, promoted by major insurance companies and the AMA, that complains about a "liability crisis" in general and specifically about a civil justice system crisis as it relates to medical malpractice. It is unfortunate that those involved in the production of this media campaign used blatantly false and misleading facts concerning specific cases and the functioning of our civil justice system. There is no question that liability insurance premiums are
MUSCLE AND TENDON INJURIES AT AN INTERNATIONAL MULTI-SPORT TOURNAMENT: EUROPEAN MACCABI GAMES 2011
Authors: Daniel Broman, Robert Fearn, Marc Wittenberg
Journal: British Journal of Sports Medicine (2013)

A multi-sport event poses a different variety of problems for a medical team, when compared to tournaments of specific sports, due to the diverse range of injuries that occur. There is a lot of data about injury rates in specific sports, but data on epidemiology of medical problems at multi-sports events is limited. Our aim was to research the injuries that occur during multi-sport tournaments, by performing a prospective cross-sectional data collection study, as the medical team covering Team GB for the European Maccabi Games 2011. We collected injury profile statistics in relation to the sport played, age of patient, ‘type’ of injury sustained, anatomical location and severity (absence from training or match). 230 athletes had 88 medical encounters over the tournament, which compromised 1405 ‘player-hours’ of sport. This means the general injury rate was 62.6 injuries per 1000 hours of sport played. Our data found that the majority of injuries sustained at multi-sport tournaments were muscle and tendon injuries, with 52/88 (59%) of our total medical encounters affecting muscles and/or tendons. The sport with the highest risk of muscle or tendon injury was football with 45% of the total injuries occurring in this event, compared to lower-risk sports (eg. swimming, bowling or fencing). Futsal had a moderate risk of injury, with 27% (14/52) of injuries occurring in this sport. Of all the muscle and tendon injuries, the majority, 73% (38/52) affected the lower limbs, 10% (5/52) affected the upper limbs and 17% (9/52) affected the back or neck. With regard to severity, 50% (26/52) were classed as an incident (no time lost from competition). Of the remaining 26 injuries that caused a player to lose playing time 54% were classed as minor (&lt;1 match missed), 31% as moderate (1–2 matches missed) and 15% as major (&gt;2 matches missed). By studying injury data, our medical team can prepare for future multi-sport events and attempt to produce injury prevention programmes.
Effectiveness of Comprehensive-Care Programs in Preventing Rheumatic Fever
Authors: Leon Gordis
Journal: New England Journal of Medicine (1973)

Four inner-city comprehensive-care programs in Baltimore were evaluated by study of their effect on incidence of rheumatic fever. Annual incidence of hospitalized first attacks was estimated for the black population five to 14 years old living in census tracts eligible for these programs in 1968–70. For comparison, incidence rates in three noneligible population groupings were calculated and compared with rates for 1960–64, before these programs were established. The rate of rheumatic fever for comprehensive-care tracts in 1968–70 was about 1/3 lower than for the rest of Baltimore. From 1960–64 to 1968–70 rheumatic fever decreased 60 per cent in comprehensive-care tracts but was unchanged in the rest of the city. The declining incidence in Baltimore resulted entirely from a reduction in preventable cases preceded by clinical respiratory infections although bacteriologic data were not available. The findings thus suggest that comprehensive-care programs have been the critical factor in reducing the incidence of rheumatic fever in the inner city. (N Engl J Med 289:331–335, 1973)
Diet and Flight Hypoxemia
Authors: James E. Hansen
Journal: Annals of Internal Medicine (1989)

Letters and Corrections15 November 1989Diet and Flight HypoxemiaJames E. Hansen, MDJames E. Hansen, MDSearch for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-111-10-859_2 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptTo the Editor: The article by Dillard and colleagues (1) and the editorial by Gong (2) aid physicians who must determine whether patients with lung disease are likely to become hypoxemic during air travel and should receive supplemental oxygen. Although several physiologic measures are recommended (all of which may not be easily available to many internists) and many variables are considered in the equations used to predict the patient's arterial oxygen tension (PaO2) during flight, neither presentation mentions a very practical and simple factor: the role of oral intake in changing alveolar oxygen tension (PAO2) and, consequently, PaO2.Rahn and...References1. Dillard T, Berg B, Rajagopal K, Dooley J, and Mehm W. Hypoxemia during air travel in patients with chronic obstructive pulmonary disease. Ann Intern Med. 1989;111:362-7. LinkGoogle Scholar2. Gong H. Advising patients with pulmonary diseases on air travel. Ann Intern Med. 1989;111:349-51. LinkGoogle Scholar3. Rahn H and Fenn W. A Graphical Display of the Respiratory Gas Exchange; The O2-CO2 Diagram. Washington, D.C.: American Physiological Society; 1955. Google Scholar4. Hansen J, Hartley L, and Hogan R. Arterial oxygen increase by high-carbohydrate diet at altitude. J Appl Physiol. 1972;33:441-5. CrossrefMedlineGoogle Scholar5. Hansen J and Claybaugh J. Ethanol-induced lowering of arterial oxyhemoglobin saturation during hypoxia. Aviat Space Environ Med. 1975;46:1123-7. MedlineGoogle Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAuthors: James E. Hansen, MDAffiliations: Harbor-UCLA Medical Center UCLA School of Medicine Torrance, CA 90509 PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited byPulmonary Function Testing and Extreme EnvironmentsAir Travel and Oxygen Therapy in Cardiopulmonary PatientsDietary Carbohydrate, Alveolar Gas, and Chronic Obstructive Pulmonary DiseaseThomas A. Dillard, MDOxygen, Food, and Air TravelRolando Berger, MD 15 November 1989Volume 111, Issue 10Page: 859-859KeywordsArterial partial pressure of oxygenDietHypoxiaLungsOxygenPartial pressure of oxygen in the alveoli ePublished: 1 December 2008 Issue Published: 15 November 1989 PDF downloadLoading ...