tbuckley/cabot-search huggingface dataset:
Alastair Hugh Bailey Masson
Authors: T. Wildsmith, E. Masson
Journal: BMJ (2010)

Alastair Hugh Bailey Masson’s career spanned anaesthesia’s development from a time when whole time practitioners were rare to the scientifically and technologically based, highly specialist practice of today. He was a leader in that development, particularly in helping to solve the problems of open heart surgery during the late 1950s and early 1960s, in promoting the highest standards of individual patient care, and in contributing to the education and training of his younger colleagues, for many of whom he was a valued source of advice and support. Primarily a clinician he nevertheless recognised the importance of research to the specialty’s development, actively encouraging and contributing to its performance. A major interest was the history of medicine, and this led to his appointment as honorary archivist to the Royal College of Surgeons of Edinburgh, a position that he filled with great distinction.

Alastair was educated at Bathgate Academy and studied Medicine in Edinburgh, so following in the footsteps of that great pioneer of anaesthesia, James “Young” Simpson. After qualifying in 1947, he applied to undertake his two years of national service in the Royal Air Force, and was soon posted to Habbaniya in Iraq, but with a brief transfer to the much smaller base of Mauripur in Pakistan. This was to prove a …
Spironolactone and risk of upper gastrointestinal events: Author's reply
Authors: Katia M Verhamme, Jeanne P Dieleman, Bruno H Ch Stricker, Miriam C J M Sturkenboom
Journal: BMJ (2006)

EDITOR—With interest, we have read the rapid responses to our article and would like to reply to some of the questions and concerns that have been raised.

Campbell et al questioned …
Intracardiac Injections During Resuscitation
Authors: Hugo Keszler
Journal: JAMA (1981)

<h3>To the Editor.—</h3> Davison et al (1980; 244:1110) recommend intracardiac injections (ICI) in cardiopulmonary resuscitation (CPR) as a safe alternative to intravenous (IV) administration of emergency drugs when other sites are not readily available. Although the subxyphoid approach is preferable to the anterior intercostal approach, we believe the article suffers from a number of serious deficiencies. There is no mention of the most important issue in this context, and that is how long CPR was interrupted during the injection. Obviously interrupting cardiac compression for more than a few seconds is highly undesirable and may adversely affect the outcome. Second, we are struck by a strange statement in the fourth paragraph under "Comment" from which it appears that positive pressure breathing was continued during cardiac puncture. Does that mean that ventilation was continued while artificial circulation was stopped? There is also no listing of which drugs were given by intracardiac route,
Recoupling the Na-K Pump
Authors: John R. Sachs
Journal: Journal of Clinical Investigation (1972)

Human red blood cells display under appropriate circumstances a ouabain-sensitive K-K exchange when the flux measurements are made using radioisotopes. Such an exchange complicates measurements of the coupling of Na outflux to K influx in cells which are partially depleted of energy sources by deprivation of glucose since the K-K exchange has been found to be increased in depleted cells. When the measurements of flux are made by estimating net cation movements chemically, it is found that glucose deprivation results in a fall in both ouabain-sensitive Na outflux and ouabain-sensitive K influx. Since both fluxes fell in concert, there is no reason for believing that the fluxes are not coupled or that the source of ATP for the Na outflux is different from that for the K influx.
Abstract 1301: Metformin induces cytotoxicity by TP and ERCC1 decrease.
Authors: Yun-Wei Lin, Yu-Ching Huang, Sheng-Chieh Tseng, Hsien-Chun Chiu, Huang-Jen Chen, Yi-Jhen Huang, Ting-Yu Wo, Shao-Hsing Weng, Jen-Chung Ko
Journal: Cancer Research (2013)

Abstract Metformin is an anti-diabetic drug recently shown to inhibit cancer cell proliferation and growth, although the involved molecular mechanisms have not been elucidated. In many cancer cells, highly expression of thymidine phosphorylase (TP) and ERCC1 are associated with poor prognosis. We used A549 and H1975 huamn non-small cell lung cancer (NSCLC) cell lines to investigate the role of TP and ERCC1 expression in metformin-induced cytotoxicity. Metformin treatment decreased cellular TP and ERCC1 protein and mRNA levels by down-regulating phosphorylated MEK1/2-ERK1/2 protein levels in a dose- and time-dependent manner. The enforced expression of the constitutively active MEK1 (MEK1-CA) vectors significantly restored cellular TP and ERCC1 protein levels and cells viability. Specific inhibition of TP and ERCC1 expression by siRNA enhanced the metformin-induced cytotoxicity and growth inhibition. In conclusion, metformin induces cytotoxicity by down-regulating TP and ERCC1 expression in NSCLC cells. Citation Format: Yun-Wei Lin, Yu-Ching Huang, Sheng-Chieh Tseng, Hsien-Chun Chiu, Huang-Jen Chen, Yi-Jhen Huang, Ting-Yu Wo, Shao-Hsing Weng, Jen-Chung Ko. Metformin induces cytotoxicity by TP and ERCC1 decrease. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 1301. doi:10.1158/1538-7445.AM2013-1301
Hyperactivation of phosphatidylinositol-3 kinase promotes escape from hormone dependence in estrogen receptor–positive human breast cancer
Authors: Todd W. Miller, Bryan T. Hennessy, Ana M. González-Angulo, Emily M. Fox, Gordon B. Mills, Heidi Chen, Catherine Higham, Carlos García-Echeverría, Yu Shyr, Carlos L. Arteaga
Journal: Journal of Clinical Investigation (2010)

Many breast cancers exhibit a degree of dependence on estrogen for tumor growth. Although several therapies have been developed to treat individuals with estrogen-dependent breast cancers, some tumors show de novo or acquired resistance, rendering them particularly elusive to current therapeutic strategies. Understanding the mechanisms by which these cancers develop resistance would enable the development of new and effective therapeutics. In order to determine mechanisms of escape from hormone dependence in estrogen receptor-positive (ER-positive) breast cancer, we established 4 human breast cancer cell lines after long-term estrogen deprivation (LTED). LTED cells showed variable changes in ER levels and sensitivity to 17beta-estradiol. Proteomic profiling of LTED cells revealed increased phosphorylation of the mammalian target of rapamycin (mTOR) substrates p70S6 kinase and p85S6 kinase as well as the PI3K substrate AKT. Inhibition of PI3K and mTOR induced LTED cell apoptosis and prevented the emergence of hormone-independent cells. Using reverse-phase protein microarrays, we identified a breast tumor protein signature of PI3K pathway activation that predicted poor outcome after adjuvant endocrine therapy in patients. Our data suggest that upon adaptation to hormone deprivation, breast cancer cells rely heavily on PI3K signaling. Our findings also imply that acquired resistance to endocrine therapy in breast cancer may be abrogated by combination therapies targeting both ER and PI3K pathways.
Transplant Estimated Function
Authors: Andrea Caumo, Paola Maffi, Rita Nano, Federico Bertuzzi, Livio Luzi, Antonio Secchi, Ezio Bonifacio, Lorenzo Piemonti
Journal: Diabetes Care (2008)

The beta-score is a highly regarded approach to the assessment of transplant functionality. Our aim was to develop an index of beta-cell function that hinges on the pillars of the beta-score (daily insulin requirement and A1C), has a straightforward physiological interpretation, and does not require the execution of an insulin stimulation test.The new index is denoted transplant estimated function (TEF) and is obtained from the daily insulin requirement and A1C. TEF estimates the amount of insulin secreted daily and can be normalized to the number of transplanted islets, thus permitting evaluation of the cost-effectiveness of the transplant. TEF was compared with the area under the curve of C-peptide [AUC(C-pep)] concentration over 24 h, as well as the acute insulin response to intravenous glucose (AIR(glu)) and to arginine (AIR(arg)). The association between TEF and beta-score was also investigated.The correlation of TEF with 24-h AUC(C-pep) was r = 0.73 (P < 0.005), whereas that for beta-score versus 24-h AUC(C-pep) was r = 0.33 (NS). The correlation of TEF with AIR(glu) was r = 0.59 (P < 0.001) and close to that for beta-score versus AIR(glu) (r = 0.65, P < 0.001). The correlation of TEF with AIR(arg) was r = 0.33 (P < 0.005) and was similar to that for beta-score versus AIR(arg) (r = 0.34, P < 0.005). TEF and beta-score were correlated well (r = 0.69, P < 0.0001) and showed similar time profiles.TEF estimates daily insulin secretion, it is simpler than the beta-score, and its performance against reference indexes of beta-cell secretion is in line with that exhibited by beta-score. TEF can be normalized to the number of transplanted islets and thereby provides a benchmarking tool to evaluate the cost-effectiveness of the transplant.
Molecular mechanisms of the defective hepcidin inhibition in TMPRSS6 mutations associated with iron-refractory iron deficiency anemia
Authors: Laura Silvestri, Flavia Guillem, Alessia Pagani, Antonella Nai, Claire Oudin, Muriel Silva, Fabienne Toutain, Caroline Kannengiesser, Carole Beaumont, Clara Camaschella, Bernard Grandchamp
Journal: Blood (2009)
CORTICOTROPIN AND CORTISONE TREATMENT FOR SYSTEMIC LUPUS ERYTHEMATOSUS
Authors: Edmund L. Dubois
Journal: JAMA (1952)

We have studied 64 patients with systemic lupus erythematosus, 30 of whom were treated with various regimens that included corticotropin (ACTH) and/or cortisone therapy. The incidence of remissions and the life expectancy in treated and untreated patients have been compared. The 34 untreated patients studied all died of systemic lupus erythematosus in the Los Angeles County Hospital during the 15 year period from January, 1935, to January, 1950. Spontaneous clinical remissions after onset of the unequivocal active disease occurred in seven of these patients. The mean duration of life after the onset of systemic lupus erythematosus in this group and in similar groups reported by Klemperer<sup>1</sup>and Tumulty<sup>2</sup>is presented in table 1. The 30 patients receiving corticotropin or cortisone were all treated in this hospital prior to July 1, 1951. The diagnosis was confirmed in each patient by one or more of the following symptoms: typical skin
HPMA copolymer conjugates with reduced anti-CD20 antibody for cell-specific drug targeting. I. Synthesis and in vitro evaluation of binding efficacy and cytostatic activity
Authors: Tomáš Etrych, Jiří Strohalm, Lubomír Kovář, Martina Kabešová, Blanka Říhová, Karel Ulbrich
Journal: Journal of Controlled Release (2009)
Serratia marcescens Endocarditis
Authors: MICHAEL SANDS
Journal: Annals of Internal Medicine (1976)

Comments1 September 1976Serratia marcescens EndocarditisMICHAEL SANDS, M.D., C. V. SANDERS, M.D.MICHAEL SANDS, M.D.Search for more papers by this author, C. V. SANDERS, M.D.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-85-3-397_2 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptTo the editor: Having read Mills and Drew's article (Ann Intern Med 84:29-35, 1976), we wish to report the case of a patient with Serratia marcescens endocarditis treated by us.A 64-year-old male heroin addict, previously well, presented complaining of dyspnea and confusion for 1 week. Positive physical findings included a temperature of 40 °C [104 °F]; sinus tachycardia, 130/min; blood pressure 118/60 mm Hg; bibasilar moist rales; and a grade iii/vi holosystolic decrescendo murmur heard at the cardiac apex, radiating to the left axilla. Leukocyte count was 14 000/mm3with 87% neutrophils; hematocrit, 32%; urinalysis showed 30 erythrocytes/high-power field;...References1. BRYAN C, MARNEY S, and ALFORD R: Gram-negative bacillary endocarditis: interpretation of the serum bactericidal test. Am J Med 58:209-215, 1975 CrossrefMedlineGoogle Scholar2. KHAN F and KHAN A: Serratia marcescens endocarditis. Am J Med 79:454, 1973 AbstractGoogle Scholar3. FARGOUDI H, BANKS T, and ALI N: A case report of Serratia endocarditis with review of the literature. Med Ann DC 43:401-406, 1974 MedlineGoogle Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAuthors: MICHAEL SANDS, M.D.; C. V. SANDERS, M.D.Affiliations: Louisiana State University Medical Center New Orleans, LA 70112 PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited byInfective endocarditis by Serratia species: a systematic reviewSerratia Marcescens, a Rare and Devastating Cause of Endocarditis: A Case Report and Review of the LiteratureEndocarditis and Intravascular InfectionsA Case of Mixed Serratia marcescens and Streptococcus mitis Endocarditis and Review of the LiteratureEndocarditis and Intravascular InfectionsACUTE INFECTIVE ENDOCARDITISSerratia Keratitis Transmitted by Contaminated EyedroppersTreatmentInfective endocarditis caused by gram-negative bacteria: A review of the literature, 1945–1977 1 September 1976Volume 85, Issue 3Page: 397-398KeywordsAddictsBlood pressureDyspneaEndocarditisHematocritHeroinNeutrophilsSerratia marcescensTachycardiaTemperature ePublished: 1 December 2008 Issue Published: 1 September 1976 PDF downloadLoading ...
Smad6 negatively regulates interleukin 1-receptor–Toll-like receptor signaling through direct interaction with the adaptor Pellino-1
Authors: Kyung-Chul Choi, Youn Sook Lee, Seunghwan Lim, Hyo Kyoung Choi, Chang-Hun Lee, Eun-Kyung Lee, Suntaek Hong, In-Hoo Kim, Seong-Jin Kim, Seok Hee Park
Journal: Nature Immunology (2006)
Distinct and Nonredundant In Vivo Functions of IFNAR on Myeloid Cells Limit Autoimmunity in the Central Nervous System
Authors: Marco Prinz, Hauke Schmidt, Alexander Mildner, Klaus-Peter Knobeloch, Uwe-Karsten Hanisch, Jenni Raasch, Doron Merkler, Claudia Detje, Ilona Gutcher, Jörg Mages, Roland Lang, Roland Martin, Ralf Gold, Burkhard Becher, Wolfgang Brück, Ulrich Kalinke
Journal: Immunity (2008)
Monocytic cell type-specific transcriptional induction of collagenase.
Authors: R A Pierce, S Sandefur, G A Doyle, H G Welgus
Journal: Journal of Clinical Investigation (1996)

Interstitial collagenase (MMP-1), a metalloproteinase produced by resident and inflammatory cells during connective tissue turnover, cleaves type I collagen fibrils. This catalytic event is rate limiting in remodeling of tissues rich in fibrillar collagen such as the skin and lungs. The regulation of collagenase expression is cell-type specific; bacterial LPS and zymosan, a yeast cell wall derivative, are potent inducers of collagenase expression in macrophages, but do not alter fibroblast collagenase expression. Since promoter elements controlling collagenase transcription in monocytic cells have not been previously defined, we sought to delineate responsive cis-acting elements of the collagenase promoter in transiently transfected human (U937) and murine (J774) monocytic cell lines. Deletion constructs containing as little as 72 bp of 5' -flanking sequence of the collagenase promoter were sufficient for LPS- or zymosan-mediated transcriptional induction, whereas phorbol inducibility exhibited an absolute requirement for upstream elements including the polyoma enhancer A-binding protein-3 site (-83 to -91) and TTCA sequence (-102 to -105) in both monocytic cells and fibroblasts. Mutagenesis of the activator protein-1 [AP-1] site at -72 abolished basal promoter activity and LPS/zymosan inducibility, while mutagenesis of an NF-kappaB-like site at -20 to -10 had no effect. Nuclear extracts from LPS- and zymosan-treated cells showed strong AP-1 activity by gel-shift analysis, and supershift analysis showed the AP-1 complexes contained specific members of both the jun and fos gene families. These data indicate that, in contrast to most LPS effects, AP-1, but not nuclear factor-kappaB, mediates LPS induction of collagenase transcription in macrophagelike cells. Furthermore, as compared to regulation by phorbol ester, collagenase induction in monocytic cells by cell wall derivatives of bacteria or yeast is largely independent of upstream promoter sequences.
Pyk2 activation is integral to acid stimulation of sodium/hydrogen exchanger 3
Authors: Shaoying Li, Soichiro Sato, Xiaojing Yang, Patricia A. Preisig, Robert J. Alpern
Journal: Journal of Clinical Investigation (2004)

The present study examines the role of Pyk2 in acid regulation of sodium/hydrogen exchanger 3 (NHE3) activity in OKP cells, a kidney proximal tubule epithelial cell line. Incubation of OKP cells in acid media caused a transient increase in Pyk2 phosphorylation that peaked at 30 seconds and increased Pyk2/c-Src binding at 90 seconds. Pyk2 isolated by immunoprecipitation and studied in a cell-free system was activated and phosphorylated at acidic pH. Acid activation of Pyk2 (a) was specific for Pyk2 in that acid did not activate focal adhesion kinase, (b) required calcium, and (c) was associated with increased affinity for ATP. Transfection of OKP cells with dominant-negative pyk2K457A or small interfering pyk2 duplex RNA blocked acid activation of NHE3, while neither had an effect on glucocorticoid activation of NHE3. In addition, pyk2K457A blocked acid activation of c-Src kinase, which is also required for acid regulation of NHE3. The present results demonstrate that Pyk2 is directly activated by acidic pH and that Pyk2 activation is required for acid activation of c-Src kinase and NHE3. Given that partially purified Pyk2 can be activated by acid in a cell-free system, Pyk2 may serve as the pH sensor that initiates the acid-regulated signaling cascade involved in NHE3 regulation.
Dental Conditions Likely to Form Sources of Infection
Authors: B. J. Rodway
Journal: BMJ (1926)

rise to 101.50 or 1020 continued.I saw him six weeks after the oniset of the adenitis.On examination it was found that he had Aive or six molar and bicuspid teeth which had been filled for five years, and when asked if they had caused trouble, said " No,
The Nuffield report: a signpost for pharmacy.
Authors: P Turner
Journal: BMJ (1986)

The Nuffield report: -a signpost for pharmacy Two years ago we reported the setting up of the Nuffield Foundation Pharmacy Inquiry and discussed some of the problems facing our pharmaceutical colleagues in the various branches of their profession.'The report of the committee of inquiry, on which there were three medical members, has now been published and, as we forecast, its conclusions and recommendations are far reaching.2The face of pharmacy will change appreciably over the next decade if they are put into effect, and they will have an impact on other health professions, including medicine.
Asymmetry of Right Ventricular Enlargement in Response to Tricuspid Regurgitation
Authors: Sandra I. Reynertson, Ramesh Kundur, G. Martin Mullen, Maria Rosa Costanzo, Thomas L. McKiernan, Eric K. Louie
Journal: Circulation (1999)

Background —Analysis of right ventricular adaptation to tricuspid regurgitation was studied in 10 heart transplant recipients following inadvertent endomyocardial biopsy disruption of the tricuspid apparatus. Methods and Results —Echocardiography demonstrated progressive diastolic right ventricular cavity enlargement (19.5±5.0 to 30.3±5.4 cm 2 , P &lt;0.0002), with disproportionate elongation along the midminor axis (3.5±0.6 to 5.0±0.5 cm, P &lt;0.001). As the right ventricle remodeled to more spherical (and less elliptical) proportions, the end-diastolic right ventricular midminor axis/long axis ratio increased significantly from 0.52±0.10 to 0.68±0.07, P &lt;0.005. Conclusions —Ventricular enlargement due to right ventricular volume overload results in disproportionate dilation along the free wall to septum minor axis.
The Safety of Iron-Fortified Food
Authors: William H. Crosby
Journal: JAMA (1978)

The addition of extraneous chemicals to our diet is a topic of acrimonious controversy. Food additives, by and large, have probably done more good than harm: iodine in salt to prevent goiter and vitamin D in milk to prevent rickets are two good examples; salt in baby food and sugar in breakfast food are two examples not so good. The fortification of food with iron is a problem more complex than most others.<sup>1</sup>It is intended to prevent iron deficiency, and the target population is among the menstruating women. Men and postmenopausal women, unless they bleed, rarely become iron deficient. The size and even the constituents of the target are not yet clearly defined. One government survey demonstrated, in a sample of 30,000 people, that 20% of the<i>men</i>had iron deficiency anemia.<sup>2</sup>Several years later, another government survey demonstrated that only 2% of the women were iron
Imaging Epidermal Growth Factor Receptor Expression <i>In vivo</i>: Pharmacokinetic and Biodistribution Characterization of a Bioconjugated Quantum Dot Nanoprobe
Authors: Parmeswaran Diagaradjane, Jacobo M. Orenstein-Cardona, Norman E. Colón-Casasnovas, Amit Deorukhkar, Shujun Shentu, Norihito Kuno, David L. Schwartz, Juri G. Gelovani, Sunil Krishnan
Journal: Clinical Cancer Research (2008)

Abstract Purpose: To develop and validate an optical imaging nanoprobe for the discrimination of epidermal growth factor (EGF) receptor (EGFR)–overexpressing tumors from surrounding normal tissues that also expresses EGFR. Experimental Design: Near-infrared (NIR) quantum dots (QD) were coupled to EGF using thiol-maleimide conjugation to create EGF-QD nanoprobes. In vitro binding affinity of these nanoprobes and unconjugated QDs was evaluated in a panel of cell lines, with and without anti-EGFR antibody pretreatment. Serial optical imaging of HCT116 xenograft tumors was done after systemic injection of QD and EGF-QD. Results: EGF-QD showed EGFR-specific binding in vitro. In vivo imaging showed three distinct phases, tumor influx (∼3 min), clearance (∼60 min), and accumulation (1-6 h), of EGF-QD nanoprobes. Both QD and EGF-QD showed comparable nonspecific rapid tumor influx and clearance followed by attainment of an apparent dynamic equilibrium at ∼60 min. Subsequently (1-6 h), whereas QD concentration gradually decreased in tumors, EGF-QDs progressively accumulated in tumors. On delayed imaging at 24 h, tumor fluorescence decreased to near-baseline levels for both QD and EGF-QD. Ex vivo whole-organ fluorescence, tissue homogenate fluorescence, and confocal microscopic analyses confirmed tumor-specific accumulation of EGF-QD at 4 h. Immunofluorescence images showed diffuse colocalization of EGF-QD fluorescence within EGFR-expressing tumor parenchyma compared with patchy perivascular sequestration of QD. Conclusion: These results represent the first pharmacokinetic characterization of a robust EGFR imaging nanoprobe. The measurable contrast enhancement of tumors 4 h after systemic administration of EGF-QD and its subsequent normalization at 24 h imply that this nanoprobe may permit quantifiable and repetitive imaging of EGFR expression.
RETRACTED ARTICLE: MEK inhibition enhances ABT-737-induced leukemia cell apoptosis via prevention of ERK-activated MCL-1 induction and modulation of MCL-1/BIM complex
Authors: M Konopleva, M Milella, P Ruvolo, J C Watts, M R Ricciardi, B Korchin, T McQueen, W Bornmann, T Tsao, P Bergamo, D H Mak, W Chen, J McCubrey, A Tafuri, M Andreeff
Journal: Leukemia (2011)