tbuckley/cabot-search huggingface dataset:
P13.23 * RADIOSENSITISATION OF PRIMARY GLIOBLASTOMA MULTIFORME CELLS FOLLOWING INHIBITION OF THE METABOLIC AUTOPHAGY PATHWAY
Authors: A. Swampillai, S. Galavotti, M. Shaked-Rabi, A. McEvoy, S. Brandner, P. Salomoni, S. Short
Journal: Neuro-Oncology (2014)

BACKGROUND: Glioblastoma multiforme (GBM) remains a challenge for clinicians due to its heterogeneity and resistance to conventional treatment with temozolomide and radiation. This may be due to GBM stem cells which have been implicated in both tumour recurrence and progression. Autophagy is an evolutionarily conserved metabolic process with dual role in carcinogenesis. It acts as a tumour suppressive mechanism in normal tissues, but promotes tumour survival upon genotoxic stress. Our previous work showed that an autophagy gene expression signature is enriched in GBM tumours belonging to the mesenchymal subtype, an association that is maintained in primary glioblastoma cells. The main objective of the present work is to investigate the role of autophagy in primary GBM cells, following a fractionated course of radiotherapy and combination treatment (TMZ and fractionated RT). METHOD: We used primary GBM cells from fully consented patients supplied by local biobanks. Autophagy was inhibited both by pharmacological means, chloroquine (CQ) and hydroxychloroquine (HCQ) and by the stable knockdown of the essential autophagy gene ATG7. Cells were irradiated using the HS X- ray systems Varian NDI- 32 .Temozolomide was used at the clinically relevant dose of 100uM. Using the cell viability SRB assay and InCucyte derived growth curves response to radiotherapy was assessed following either a single 5 Gy fraction or a fractionated schedule of 10Gy in 5 fractions. RESULTS: Inhibition of autophagy using CQ/HCQ/knockdown did not significantly alter growth characteristics of primary GBM cells at steady state, as demonstrated by growth curves. Using clinically relevant schedules of fractionated radiotherapy, we demonstrated a statistically significant radiosensitisation upon autophagy inhibition, which was not seen following a single 5Gy treatment. This effect was seen regardless of the method of autophagy inhibition and persisted when cells co-treated with TMZ underwent fractionated radiotherapy. CONCLUSION: There are currently a large number of clinical trials based on the inhibition of the metabolic autophagy pathway, using CQ and HCQ. Our work implicates autophagy in resistance to radiotherapy in primary GBM cells and suggests that autophagy inhibition will be an effective means of improving outcome of radiotherapy. A randomised phase II study investigating the role of HCQ to inhibit autophagy in addition to short course radiotherapy in patients aged 70years and older with GBM and is open to recruitment at our institution (NCT01602588).
Magnetic field-controlled gene expression in encapsulated cells
Authors: Viktoria Ortner, Cornelius Kaspar, Christian Halter, Lars Töllner, Olga Mykhaylyk, Johann Walzer, Walter H. Günzburg, John A. Dangerfield, Christine Hohenadl, Thomas Czerny
Journal: Journal of Controlled Release (2011)

Cell and gene therapies have an enormous range of potential applications, but as for most other therapies, dosing is a critical issue, which makes regulated gene expression a prerequisite for advanced strategies. Several inducible expression systems have been established, which mainly rely on small molecules as inducers, such as hormones or antibiotics. The application of these inducers is difficult to control and the effects on gene regulation are slow. Here we describe a novel system for induction of gene expression in encapsulated cells. This involves the modification of cells to express potential therapeutic genes under the control of a heat inducible promoter and the co-encapsulation of these cells with magnetic nanoparticles. These nanoparticles produce heat when subjected to an alternating magnetic field; the elevated temperatures in the capsules then induce gene expression. In the present study we define the parameters of such systems and provide proof-of-principle using reporter gene constructs. The fine-tuned heating of nanoparticles in the magnetic field allows regulation of gene expression from the outside over a broad range and within short time. Such a system has great potential for advancement of cell and gene therapy approaches.
Points: Does wearing two pairs of gloves protect against skin contamination?
Authors: A W Fowler
Journal: BMJ (1988)

American Society of Anaesthesiologists' (ASA) grade system (ASA I, healthy patient; ASA II, mild systemic disease; ASA III, severe, non- incapacitating systemic disease; ASA IV, severe, incapacitating systemic disease which is a constant threat to life; and ASA V, moribund patient, not expected to live for 24 hours with or without surgery) abnormal values were found in 1-5% of patients in grade I, 17% in grade II, 35% in grade III, and 48% in grades IV and V.' In addition, most abnormal values in patients in grade II were minor and not clinically important.Therefore patients in grades I and II do not need routine estimations of urea and electrolyte concentrations whereas those in grades III, IV, and V do, as the results are much more likely to be abnormal.I therefore suggest that this grading system, which could be easily learnt by junior medical staff, would be more appropriate than age as an indicator of the need for biochemical screening preoperatively.
CHEMICAL, CLINICAL, AND IMMUNOLOGICAL STUDIES ON THE PRODUCTS OF HUMAN PLASMA FRACTIONATION. XXII. FIBRIN FILMS IN NEUROSURGERY, WITH SPECIAL REFERENCE TO THEIR USE IN THE REPAIR OF DURAL DEFECTS AND IN THE PREVENTION OF MENINGOCEREBRAL ADHESIONS 12
Authors: Orville T. Bailey, Franc D. Ingraham
Journal: Journal of Clinical Investigation (1944)
Is the Skin Prick Test (SPT) for milk useful for diagnosis of Cow's Milk Allergy (CMA) in infants?
Authors: V.P. Oliveira, A.B.M. Castro, A.P.M. Pegas, A.K. Gushken, A.C. Pastorino, Â.B.F. Fomin, C.M.A. Jacob
Journal: Journal of Allergy and Clinical Immunology (2009)
Why Are Cholecystectomy Rates Increasing?
Authors: David F. Ransohoff, Charles K. McSherry
Journal: JAMA (1995)

Although the laparoscopic approach to cholecystectomy was introduced only about 5 years ago, it now accounts for some 90% of all cholecystectomies done in the United States. Following the introduction of this type of "minimally invasive surgery," the overall number of procedures has increased by about 22%, at least in the elderly in Pennsylvania described in this issue of<i>JAMA</i>by Escarce et al.<sup>1</sup>What is the explanation for this change in practice behavior, and is the change for the better? See also p 1581. The laparoscopic approach clearly is more convenient than the open approach to cholecystectomy because it requires shorter hospital stay and allows quicker return to work. Indeed, the rapid and widespread adoption of laparoscopic cholecystectomy appears to have been in large part patient driven because of the procedure's convenience. The laparoscopic approach is believed to be as safe as or perhaps safer than open cholecystectomy,
Effects of montelukast (MK-0476), a new potent cysteinyl leukotriene (LTD4) receptor antagonist, in patients with chronic asthma☆, ☆☆, ★, ★★
Authors: T REISS, L ALTMAN, P CHERVINSKY, A BEWTRA, W STRICKER, G NOONANA, S KUNDU, J ZHANG
Journal: Journal of Allergy and Clinical Immunology (1996)
Intracellular re-localisation by photochemical internalisation enhances the cytotoxic effect of gelonin — Quantitative studies in normal rat liver
Authors: Josephine Woodhams, Pei-Jen Lou, Pål K. Selbo, Alexander Mosse, Dahmane Oukrif, Alexander MacRobert, Marco Novelli, Qian Peng, Kristian Berg, Stephen G. Bown
Journal: Journal of Controlled Release (2009)
Which is more dangerous--cycling or flying?
Authors: J. Forrester
Journal: BMJ (1983)

Drs Hockings and Ballinger, cause daytime dopiness and impaired judgment.Very short acting hypnotics should now be distinguished and their potential problems recognised.If the doctor feels impelled to prescribe a hypnotic then he must strike a balance, and at present the best choice would appear to be a benzodiazepine with an elimination half life of around 10 hours (it may take longer in the elderly): long enough to sustain sleep without leading to appreciable daytime dopiness, yet leaving sufficient in the tissues to prevent withdrawal phenomena pending any next dose, or at least to moderate withdrawal features by avoiding a precipitous fall in tissue con- centrations.
Influence of terbutaline on natural killer cell activity
Authors: B. Stenius‐Aarniala, E. Vesterinen, K. Kiviranta, T. Timonen
Journal: Allergy (1988)

Studies on the effect of cAMP‐inducing agents on NK activity have been contradictory. The aim of this study was to investigate the acute effects of beta‐agonists on NK activity in vivo in 15 asthmatics and 3 healthy volunteers. Blood samples of NK activity were taken at regular intervals after placebo and after subcutaneous injection of 7 μg/kg of terbutaline. NK activity was measured by the standard 4‐h Chromium 51 release assay against the leukemic line K 562 at a 50:1 effector/target cell ratio. Compared with placebo, terbutaline induced within 30–60 min a significant increase in NK activity which lasted less than 2 h. Further studies are necessary to investigate the effect of long‐term beta‐agonist treatment on NK activity.
Abstract 535: IGF-I stimulates amino acid transporter xC- function to reduce intracellular ROS level and promote proliferation in human breast cancer cells.
Authors: Yuzhe Yang, Marc A. Becker, Douglas Yee
Journal: Cancer Research (2013)

Abstract Our laboratory identified SLC7A11/xCT as an IGF-I-induced gene specifically regulated through the adaptor protein IRS-1 in breast cancer cells. xCT encodes the functional subunit of the heterodimeric plasma membrane transport system xC-, which is critical for the cellular uptake of cystine in exchange for intracellular glutamate. xC- transporter is involved in the regulation of proliferation, metastasis, and treatment resistance in cancer. To determine the role for xC- expression in IGF-mediated breast cancer cell biology, two classes of breast cancer cell lines were studied: estrogen receptor (ER) positive cell lines (IRS-1 activated) MCF-7, ZR-75-1, and T47D; basal-like cell lines (IRS-2 activated) MDA-MB-231, BT549, and HS578T. Significantly increased xCT mRNA expression was observed only in ER positive cell lines, which was eliminated by IRS-1 specific siRNA (25 nM). IGF-I increased xCT protein expression measured by immunblots and flow cytometry only in ER positive cells in an IRS-1 dependent manner. To measure the function of upregulated xC-, extracellular levels of glutamic acid and intracellular level of total glutathione were measured in MCF-7 and MDA-MB-231. IGF-I regulated xC- transporter function only in IRS-1 activated MCF-7 cells. In MCF-7 cells, IGF-I-stimulated monolayer and anchorage-independent growth were suppressed by treating cells with xCT shRNA or the xCT chemical inhibitor sulfasalazine (SASP, 0.1 mM). Direct measurement of reactive oxygen species (ROS) and levels of phospho-p38MAPkinase showed that IGF-I reduced cellular ROS level (induced by 10 Gy of irradiation or 1 ug/ml of mitomycin C), SASP (0.1 mM) reversed this IGF-I effect. Anchorage-independent growth assays suggested that inhibiting xC- function by 0.1 mM SASP sensitized the response of MCF-7 cells to anti-IGF-IR monoclonal antibody humanized EM164 (ImmunoGen, Inc.) and tyrosine kinase inhibitor NVP-AEW-541. These data suggest that IGF-I promotes the proliferation of ER positive breast cancer cells by regulating xC- transporter function in an IRS-1 dependent manner. Furthermore, IGF-I protects cells from ROS via upregulation of xC-. Our findings also imply that combination of xC- transporter inhibitor with anti-IGF-IR agents may have synergic therapeutic effects. Citation Format: Yuzhe Yang, Marc A. Becker, Douglas Yee. IGF-I stimulates amino acid transporter xC- function to reduce intracellular ROS level and promote proliferation in human breast cancer cells. [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 535. doi:10.1158/1538-7445.AM2013-535
Genetic counseling and testing for breast-ovarian cancer susceptibility: what do women want?
Authors: J Audrain, B Rimer, D Cella, J Garber, B N Peshkin, J Ellis, J Schildkraut, M Stefanek, V Vogel, C Lerman
Journal: Journal of Clinical Oncology (1998)

PURPOSE To assess preferences for the content and process of genetic counseling and testing for breast-ovarian cancer susceptibility among women at high risk for breast cancer. METHODS Ninety-eight healthy women who had a family history of breast cancer in at least two first-degree relatives participated in a structured telephone survey that evaluated preferences for type of provider and the content and process of pretest education and posttest genetic counseling. RESULTS Forty-two percent of women preferred that pretest education be delivered by a genetic counselor, while 22% preferred an oncologist. This preference was positively associated with a desire to discuss psychosocial issues during the session (P = .001). For posttest counseling, 38% of women preferred an oncologist, while 20% preferred a genetic counselor. However, women who desired supportive counseling during this session were significantly more likely to prefer a genetic counselor to an oncologist (P = .02). Fewer women wished to see a primary care physician or gynecologist for pretest education (11%) or posttest counseling (22%). With regard to the counseling process, 82% of women wished to self-refer for genetic counseling, but 63% desired advice and recommendations about whether to be tested. CONCLUSION When feasible, the optimal approach may be for oncologists to work with genetic counselors to provide pretest education and medical recommendations. Elicitation of patients' preferences may be useful to determine the level of counseling services needed.
John H. Talbott, MD: 10th JAMA Editor
Authors: Phil Gunby
Journal: JAMA (1990)

JOHN HAROLD TALBOTT, MD, 10th editor of<i>JAMA</i>, is dead at the age of 88 years. "It's a long way from Grinnell [Iowa, his birthplace] to Delray [Beach, Fla, where he died of lymphoma October 10]," he told interviewer Nancy Yanes Hoffman, PhD, 7 years ago (<i>JAMA</i>. 1983;249:2606-2612), "and it's been a good journey, every step of the way." With him through much of that journey, and surviving him, is his wife of 59 years, the former Florence Mildred Cherry, whom he met when he was an intern at Presbyterian Hospital in New York and she was a nursing student. Other survivors include their son, John Andrew Talbott, MD, professor and chair, Department of Psychiatry, University of Maryland, Baltimore; daughter, Cherry, Glenwood Springs, Colo; four grandchildren; and two of his three brothers. All four brothers attended Grinnell College and went on to graduate schools at Harvard where, perhaps influenced by
Diagnostic medicine gains from DNA probes
Authors: Kathryn Simmons
Journal: JAMA (1985)

Although they've been in use for nearly a decade, deoxyribonucleic acid (DNA) probes are now becoming a research tool with seemingly endless applications for medicine. Among their uses are prenatal diagnosis, detection of pathogens, and diagnosis and typing of viral infections.  Referring to their ability to identify one molecule from hundreds of thousands of messenger ribonucleic acid (RNA) strands, one investigator has called  use of DNA probes the magnet to pull  needle out of  haystack.  DNA probes are specific, single-stranded nucleic acid sequences that are used to search for complementary sequences from a pool of single-stranded DNA. Their construction takes advantage of recombinant DNA technology, and as such they are manipulatable laboratory tools. A recent review article on DNA in medicine ( Lancet 1984;II:908-911) outlines three ways to obtain a probe.  The first is used when  amino acid sequence of a gene product (a protein) is known.
Beyond the TV eye
Authors: J. Warden
Journal: BMJ (1988)

Television in the Commons will be a powerful force but it can never reach the parts that really need to be illuminated. How long, for instance, will it dwell on health topics even at the present high level of interest? Three minutes on a good day, perhaps? Adding vision to sound does not equal understanding. The Prime Minister was probably right when she said that a televised House would be quite different from the Commons as it is now. Whether for better or worse we shall know in due time, but the very day that the House voted the cameras in was itself full of exactly the kind of activity that is beyond their comprehension. Consider, for a start, a parliamentary device that Mrs Thatcher has newly invented in response to the health crisis. Like every such innovation it deserves to be recognised with a label of its own. I shall call it the Filofax reply. This is the Prime Minister's successful technique for turning the tables on opposition MPs who try to rattle her with hostile questions about health care deficiencies in their area. On that day, when television was the issue, the twice weekly health hype came from the Labour MPs for Bolso ver, Coventry, and Oldham, but they could as well have been from Birmingham, Newcastle, or Aberdeen. All would receive the Filofax reply. Unlike the usual all purpose parliamentary answer the Filofax reply is precisely targeted on the questioner's constituency. On the flick of a page the Prime Minister can pinpoint every pound spent on health. Thus even a hardened veteran like Mr Skinner from Bolsover, far from catching the Prime Minister out, merely gives her the chance to hit a boundary on his home ground by pointing out that phase one of the Chesterfield and North Derbyshire Royal Hospital, opened by the Queen in March 1985, provides 500 medical and surgical beds and cost ?29 million. One opponent was so frustrated that he tried to pre-empt the Filofax reply by prefacing his question with: As the Prime Minister has probably come armed with details of the new hospital to be built in my constituency.... He merely invited confirmation. A televised Commons concerned only with face values would be blind to such instances of parliamentary gamesmanship, but they do illustrate the futility of the mainstream political debate. The opposition's complaints and the Premier's Filofax replies are equally valid. Both the government and its critics are correct. So we have to dig deeper, as did the social services select committee last week when it summoned from the coalface two district general managers, Mr David Jackson from Grimsby and Dr Ken Grant of City and Hackney Health Authority. Three days ago the committee was due to complete its hearings with evidence from DHSS officials.
On the Mechanism of Vascular Leakage Caused by Histamine-Type Mediators
Authors: GUIDO MAJNO, VIRGINIA GILMORE, MONIKA LEVENTHAL
Journal: Circulation Research (1967)

A current hypothesis maintains that the vascular leakage induced by histamine, serotonin, and bradykinin is brought about by a hydrostatic mechanism: The larger veins are said to contract; the venules are therefore submitted to an increase in pressure, which causes their wall to give way. To test this hypothesis, vessels of an exposed striated muscle (rat and rabbit cremaster) were photographed while treated with the above-mentioned substances; the occurrence of vascular leakage was tested by the intravenous injection of carbon black (carbon labeling). All animals were under barbiturate anesthesia, given a neuromuscular blocking agent (gallamine triethiodid), and were maintained by artificial respiration, according to a technique previously described. In 72 rats and 4 rabbits, the first event observed was arteriolar dilatation. Constriction of a small vein was observed in only 1 in 76 experiments (in two other cases it was doubtful). It is concluded that venous spasm cannot account for the leakage induced by the mediators of the histamine type, though such leakage may be enhanced by venous spasm whenever it may occur. An alternative mechanism is proposed and discussed: Histamine-type mediators cause vascular leakage by a direct effect on the venular endothelium, which is induced to contract.
STATE AND VETERANS ADMINISTRATION COOPERATION TOWARDS BETTER MENTAL HEALTH
Authors: HARVEY J. TOMPKINS
Journal: American Journal of Psychiatry (1954)

The requirements of the Veterans Administration psychiatric program are similar to those of all organizations interested in mental health. We need to devise methods to improve the understanding and acceptance of mental illnesses. Specifically, the understanding and acceptance of the individual psychiatric patient by the man in the street, legislators, and by Medicine itself. The degree of success in improving our public relations will determine, in large part, our ability to lessen the critical need for more and better-trained mental health personnel, and increase the opportunities for research. Our accomplishments will be greater if there are cooperative efforts; indeed, with our tremendous mental health commitments and limited resources, it is doubly necessary that we use efficiently and effectively what is available to us. Cooperation must be more than an appealing word. Since mental hospitals and clinics are for the most part public agencies, there is unique opportunity here for cooperation between government levels. It is, of course, necessary that each governmental unit retain its integrity, its autonomy, and its right to shape itself to meet its particular mission. When we speak of cooperation here, we do not, therefore, mean any organic integration. We do mean a pooling of professional resources, if this is advantageous to both, and a willingness on the part of each to perform such professional activities on behalf of the other, as it can be reasonably asked to do. Two pertinent recommendations have been made by the Advisory Committee to the Psychiatry and Neurology Service of the Veterans Administration, a Committee composed of educators and practitioners in the disciplines of psychiatry, neurology, clinical psychology, social service, and nursing: "1. It is believed by the Committee that it is now desirable to bring together information about existing on-going collaboration between the Veterans Administration and the community in the area of mental health, and ideas for further collaboration which have not yet been put into practice. A survey should be undertaken jointly by appropriate organizations or agencies to bring together such knowledge and report it in such form as would be provocative to officials, helpful in planning specific collaborations, and provide material for formulation of policies governing collaborations. "2. In order that these thoughts of collaborative efforts) may be more than pious hopes, it is suggested that in every state a Mental Health Council be formed, composed of representatives of all the agencies interested in mental illness (or even broader). Such a Council would be a medium of exchange and planning and assume no operating functions. It would meet regularly. Participation in this, and encouragement by the Veterans Administration, is a second specific recommendation of the Committee."
Counterfeits of impotence drug appear in the United Kingdom
Authors: Liza Gibson
Journal: BMJ (2004)

Counterfeit versions of the erectile dysfunction treatment tadalafil (Cialis) have been found in the United Kingdom's legitimate supply chain. This is the first such occurrence since the discovery of fake versions of the ulcer drug ranitidine (Zantac), packaged as Azantac, in 1994.

The Medicines and Healthcare Products Regulatory Agency issued a drug alert last week informing healthcare professionals of two fake batches of Cialis (20 mg; lot numbers A031410 and A041410).

However, it is not known how many counterfeit tablets have entered the supply chain or how many …