tbuckley/cabot-search huggingface dataset:
Short-circuiting Oncogenes May Become Basis of New Cancer Therapies
Authors: Beverly Merz
Journal: JAMA (1989)

NEW APPROACHES to cancer therapy that target environments conducive to oncogene expression rather than the genes themselves may be on the horizon. That was the impression conveyed by two speakers at the 12th Annual Bristol-Myers Symposium on Cancer Research, held recently in Toronto, Canada. Implicit in their message was that the proteins for which oncogenes code have a variety of functions that, if properly understood, can be intercepted to reverse, and even avert, malignancy. That line of reasoning makes sense, given that each of the 60 or so known oncogenes codes for a protein that has a normal cellular function. The knowledge that oncogenes are normal cellular genes rather than viral genes inserted via retroviral infection stems from work done during the late 1970s by J. Michael Bishop, MD; Howard Varmus, MD; and Dominique Stehlin, PhD. Their experiments at the University of California, San Francisco, established the paradigm that oncogenes
Certain styrene oligomers have proliferative activity on MCF-7 human breast tumor cells and binding affinity for human estrogen receptor.
Authors: K I Ohyama, F Nagai, Y Tsuchiya
Journal: Environmental Health Perspectives (2001)

To examine the estrogenic activities of styrene oligomers, we carried out cell proliferation assays with estrogen-sensitive MCF-7 cells and competitive binding assays to human estrogen receptor [alpha] (hER[alpha]). The styrene oligomers tested were 1,3-diphenyl propane (SD-1), 2,4-diphenyl-1-butene (SD-2), cis-1,2-diphenyl cyclobutane (SD-3), trans-1,2-diphenyl cyclobutane (SD-4), 2,4,6-triphenyl-1-hexene (ST-1), 1a-phenyl-4a-(1'-phenylethyl)tetralin (ST-2), 1a-phenyl-4e-(1'-phenylethyl)tetralin (ST-3), 1e-phenyl-4a-(1'-phenylethyl)tetralin (ST-4), 1e-phenyl-4e-(1'-phenylethyl)tetralin (ST-5), 1e,3e,5a-triphenylcyclohexane (ST-6), and 1e,3e,5e-triphenylcyclohexane (ST-7). In the MCF-7 cell proliferation assay, styrene trimers (ST-1, ST-3, ST-4, and ST-5) had the highest proliferative activities of the compounds tested. The relative potency of these chemicals was 0.0002-0.0015%, which was comparable with that of bisphenol A (0.0001-0.0025%), and their relative proliferative effect was 51-104%. Styrene dimers (SD-3 and SD-4) also significantly increased the cell yields. However, SD-1, SD-2, ST-2, ST-6, and ST-7 had insignificant proliferative activities. The competitive binding assay revealed the binding affinity of some styrene oligomers for hER[alpha]. The order of their binding potency for hER[alpha] was as follows: ST-4 > ST-2 > ST-3 > ST-5 > ST-1 > SD-3 > SD-4 > SD-2 > SD-1. ST-6 and ST-7 did not appear to bind to hER[alpha]. The present studies indicate that styrene dimers SD-3 and SD-4 and styrene trimers ST-1, ST-3, ST-4, and ST-5 have estrogenic activity on MCF-7 cells and binding affinity for hER[alpha]. These compounds might be endocrine disrupters.
Atenolol, sustained-release oxprenolol, and long-acting propranolol in hypertension.
Authors: J C Petrie, T A Jeffers, O J Robb, A K Scott, J Webster
Journal: BMJ (1980)

The effect of once-daily atenolol, sustained-release oxprenolol (a new formulation of oxprenolol presented as a compressed tablet in a waxed matrix), and long-acting propranolol (a new formulation presented as spheriods in a capsule) was studied in a double-blind crossover trial in 23 carefully selected hypertensive outpatients. After a run-in period with matching placebo each patient received atenolol (100 mg/day), sustained-release oxprenolol (160 mg/day), long-acting propranolol (160 mg/day), and placebo according to a randomised sequence. After four weeks9 treatment with sustained-release oxprenolol blood pressure in the two to four hours before the next dose was not significantly lower than after placebo. The effectiveness of atenolol and of the new formulation of propranolol in reducing blood pressure was confirmed. These results suggest that the present formulation of sustained-release oxprenolol should be reconsidered.
Where are we in risk assessment of food allergens? The regulatory view
Authors: Charlotte Madsen
Journal: Allergy (2001)

Assessing the risk of exposure to chemicals is done every day worldwide. This assessment includes hazard identification, dose (concentration)-response (effect) assessment, exposure assessment and risk characterization. The present paper discusses the possibilities and limitations of using these procedures when assessing the risk of food allergens. It is concluded that hazard identification is not a problem. The medical literature is full of descriptions of cases of food allergy where the offending food or even allergen is identified. More knowledge on the relationship between dose and response of different allergens in different patient populations is needed. Exposure assessment is possible but may not be easy. Determining the distribution of contamination with an allergen may be crucial. To do risk characterization, and as a consequence to be able to manage risk, knowledge of a threshold for effect is needed and the possibility of using a safety factor. If we do not manage to establish thresholds for elicitation of allergic response in food allergy, risk assessment and management will be very difficult. It will be difficult to avoid labeling like "May contain peanuts" used with and without reason. In the long run, unjustified warnings will not help the allergic consumer but will create more confusion than guidance.
Natural orifice transluminal endoscopic surgery: cardiopulmonary safety of transesophageal mediastinoscopy
Authors: S. von Delius, D. Wilhelm, H. Feussner, J. Sager, V. Becker, T. Schuster, A. Schneider, R. Schmid, A. Meining
Journal: Endoscopy (2010)

See also: Commentaire de travail de S. von Delius et al., pp. 405Endoscopy 2010; 42(05): 434-434DOI: 10.1055/s-0031-1291859
France battles out bioethics bill
Authors: A Dorozynski
Journal: BMJ (1994)

France moved another step closer to having legislation on bioethics when three bills on the subject were passed by the senate last week. The bills were first introduced by the National Ethics Committee 10 years ago and have been passing back and forth between the national assembly and the senate for the past two years. The assembly is expected to give its final seal of approval this spring.

After two weeks of debates senators have adopted legislation that is weaker than earlier proposals. It leaves more room than was expected for personal judgment by doctors and researchers.

The first bill, drafted by the Ministry of Justice, covers general issues. It bans eugenics and allows somatic genetic treatment but not the genetic manipulation of germ cells. It opposes any patenting of the human genome and says that techniques for identifying genes must be used only in criminal investigations. As …
Confrontation Visual-Field Testing
Authors: August L. Reader
Journal: JAMA (1976)

To the Editor.—  A letter to the editor entitled, Homonymous Hemianopsia? Does Confrontation Get You Down? (235:908, 1976) told how one could check visual fields by holding the index finger of each hand out to each side at 180° and asking the patient which finger is wiggling. We would like to make a few observations about this technique and give suggestions for performing more accurate confrontation visual fields.  First, we would like to point out an inherent disadvantage in the use of wiggling fingers for the testing of visual fields. We must keep in mind that in checking confrontation fields, we are attempting to detect lesionsearlyin their clinical course, when they may be more amenable to therapy. The main disadvantage of a wiggling finger is that the movement causes enough stimulation in the affected visual field to make it easily detectable, even in the presence of moderate field-suppression.
Leadership, facilitation, and relationships are key to countering the waning influence of public health
Authors: K. A. Oliver
Journal: BMJ (2013)

<h3>Introduction</h3> The COVID-19 global pandemic has posed enormous threats to public health around the world. Vaccines are considered the best therapeutic strategy against the COVID-19 pandemic. However, the adverse reactions of vaccines significantly affect the rates of vaccination and may be more serious in patients with non-communicable diseases (NCDs). This protocol aims to conduct a systematic review and meta-analysis of randomised controlled trials (RCTs) which analysed the safety of vaccines in patients with NCDs. <h3>Methods and analysis</h3> This study will be according to the guidelines of the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols. A comprehensive search will be carried out to identify registered RCTs in PubMed, Embase, Web of Science, ClinicalTrials.gov and Cochrane Library between 1 January 2020 and 31 May 2022. Selection of trials, data extraction, risk of bias assessment and quality of evidence assessment will be done by two researchers, and disagreements will be resolved by the corresponding author. The primary outcomes are local and systemic adverse events of vaccines in patients with NCDs. Additional outcomes are related events caused by vaccine adverse events, including but not limited to cases of adverse events leading to discontinuation from a dose or withdrawal from participation in the trial. Heterogeneity will be assessed with I<sup>2</sup> statistics and data analysis will be conducted with RevMan V.5.4.1. <h3>Ethics and dissemination</h3> This is a protocol and ethical approval is not necessary. The results of this protocol will be disseminated to peer-reviewed publications or conference presentations. <h3>PROSPERO registration number</h3> CRD42021254914.
Abstract 4232: Increased sensitivity in whole-genome bisulfite sequencing (WGBS): A novel “post-bisulfite conversion” library construction method from sub-nanogram DNA inputs.
Authors: Roy Sooknanan, John Hitchen, Nick Caruccio
Journal: Cancer Research (2013)

Abstract Genome-wide analysis of 5-methylcytosines is possible with whole-genome bisulfite sequencing (WGBS), where unmethylated cytosine residues are converted to uracil. However, a major challenge in WGBS is the degradation of DNA that occurs during bisulfite conversion under conditions required for complete conversion. Typically, ∼90% of input DNA is degraded and thus, is especially problematic with limited starting amounts of DNA. Additionally, regions that are rich in unmethylated cytosines are more sensitive to strand breaks. As a consequence, a majority of DNA fragments contained in di-tagged NGS DNA libraries treated with bisulfite “post-library construction” can be rendered inactive due to strand breaks in the DNA sequence flanked by the adapter sequences. These mono-tagged templates are then excluded during library enrichment resulting in incomplete coverage and bias when performing whole genome bisulfite sequencing. Here, we describe a novel “post-bisulfite conversion” library construction method for preparing NGS libraries from genomic DNA prior to the addition of one or both adapters. This “post-bisulfite conversion” library construction method uses the resulting untagged or mono-tagged single-stranded DNA as template for the subsequent addition of adapter sequences required for NGS. Thus, single-stranded DNA fragments independent of size and position of strand breaks remain as viable templates for library construction, eliminating the loss of fragments and the selection bias associated with a “post-library construction” bisulfite conversion strategy. This novel “post-bisulfite conversion” library construction method exhibits high diversity, increased efficiency and sensitivity (500 picograms human genomic DNA input), and improved coverage required for WGBS. Citation Format: Roy Sooknanan, John Hitchen, Nick Caruccio. Increased sensitivity in whole-genome bisulfite sequencing (WGBS): A novel “post-bisulfite conversion” library construction method from sub-nanogram DNA inputs. [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 4232. doi:10.1158/1538-7445.AM2013-4232
The Effects of Competition on Prescription-Drug–Product Substitution
Authors: John E. Kralewski, Laura Pitt, Bryan Dowd
Journal: New England Journal of Medicine (1983)

Almost all states have enacted legislation, that allows pharmacists to substitute drug products when filling prescriptions. We studied the effects of competition in the drugstore service area on the use of less costly drug products and the pricing of prescriptions under the drug-product-selection law in Minnesota. In 38 drugstores in the Minneapolis-St. Paul area, rates of substitution of generic or less-costly brands and prescription prices were analyzed according to the degree of competition in the drugstore's service area, as measured by the pharmacists' perceptions and the number of competing drugstores within a 1-mile radius. Although higher levels of competition were associated with increased use of generic drugs for prescriptions written generically, competition did not appear to affect either dispensing patterns for prescriptions written for brand-name products or the retail prices of brand-name or generic products. These findings do not support the hypothesis that competition reduces prescription-drug prices through improved selection of drug products at the retail pharmacy level.
Cortical Blindness and Acute Myocardial Infarction Following Injection of Bleeding Gastric Varices with Cyanoacrylate Glue
Authors: A. P. Upadhyay, R. Ananthasivan, S. Radhakrishnan, G. Zubaidi
Journal: Endoscopy (2005)

N-butyl-2-cyanoacrylate (Histoacryl) has been in use for almost 20 years for acute control of hemorrhage from gastric varices [1]. We present here a rarely reported complication associated with its use.
Successful Management of the Sézary Syndrome
Authors: Richard Edelson, Michael Facktor, Alan Andrews, Marvin Lutzner, Philip Schein
Journal: New England Journal of Medicine (1974)

NEOPLASTIC thymus-derived (T) lymphocytes often have a characteristic tissue distribution.1 Unlike the abnormal bone-marrow-derived (B) lymphocytes of classic chronic lymphocytic leukemia and lymphosarcoma-cell leukemia,2 3 4 5 6 the leukemic T cells in the Sézary syndrome1 , 7 , 8 and in an unclassified leukemia9 preferentially infiltrate the skin and remarkably spare the bone marrow. Similarly, the neoplastic T cells in mycosis fungoides,1 a disorder probably related to the Sézary syndrome,10 11 12 characteristically localize in the skin, forming plaques and tumors.Many of the clinical sequelae of these T-cell neoplasms result from accumulation of malignant cells in extravascular sites; therefore, a prime therapeutic goal in their management is removal . . .
Early Detection of Prostate Cancer
Authors: Stephen L. Winters
Journal: Annals of Internal Medicine (1997)

Letters15 October 1997Early Detection of Prostate CancerStephen L. Winters, MDStephen L. Winters, MDMorristown Memorial Hospital; Morristown, NJ 07962-1956Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-127-8_Part_1-199710150-00030 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail TO THE EDITOR:The recently published clinical guidelines for early detection of prostate cancer [1-3] deserve unprecedented recognition. As a physician, I recently had to direct my 72-year-old father through appropriate counseling after low-grade prostate adenocarcinoma was diagnosed from biopsy specimens obtained as a result of prostate-specific antigen (PSA) screening. Fortunately, physicians with impeccable experience and integrity and outstanding communication skills have helped guide him. Unfortunately, most patients do not have the benefit of a family member or advocate who can seek unbiased opinions. Such persons may therefore be unnecessarily subjected to a physician's attitude that once the disease is ...References1. Coley CM, Barry MJ, Fleming C, Mulley AG. Early detection of prostate cancer. Part I: prior probability and effectiveness of tests. Ann Intern Med. 1997; 126:394-406. Google Scholar2. Coley CM, Barry MJ, Fleming C, Fahs MC, Mulley AG. Early detection of prostate cancer. Part II: estimating the risks, benefits, and costs. Ann Intern Med. 1997; 126:468-79. Google Scholar3. American College of Physicians. Screening for prostate cancer. Ann Intern Med. 1997; 126:480-4. Google Scholar4. Kornblith AB, Herr HW, Ofman US, Scher HI, Holland JC. Quality of life of patients with prostate cancer and their spouses. The value of a data base in clinical care. Cancer. 1994; 73:2791-802. Google Scholar Author, Article, and Disclosure InformationAuthors: Stephen L. Winters, MDAffiliations: Morristown Memorial Hospital; Morristown, NJ 07962-1956 PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 15 October 1997Volume 127, Issue 8_Part_1 Page: 656-657 ePublished: 15 August 2000 Issue Published: 15 October 1997 Copyright & PermissionsCopyright © 1997 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
Clinical Comparison of Thiopentone and Methohexitone
Authors: J. G. Whitwam, J. M. Manners
Journal: BMJ (1962)

During the past seven years there have been over 8,000 attendances at the out-patient cystoscopy clinic at the General Infirmary at Leeds, the age of the patients ranging from 8 to 78 years.Nearly all these patients have received general anaesthesia for cystoscopy, retrograde pyelography, or passage of sounds.Wherever possible, thiopentone has been used as the sole anaes- thetic agent, providing adequate operating conditions in most cases.Initial observations on the pharmacology of metho- hexitone were made in the U.S.A. in 1956, and it was introduced into clinical practice in the United Kingdom in December, 1960.The formulae of the two drugs are: O H 1 1 C2H C-N C C=S '/\ / CH3-CH2-CH2-CH C-N 1 1 CH3 I Na Sodium 5-ethyl-5-(1-methylbuty1)-2thiobarbiturate.(Thiopentone.) 0CH, 1 1 CH2 CH-CH2
Production, characterization, and expression of neuropeptide Y by human pheochromocytoma.
Authors: P deS Senanayake, J Denker, E L Bravo, R M Graham
Journal: Journal of Clinical Investigation (1995)

Neuropeptide Y (NPY) levels are increased in plasma and tumors of patients with pheochromocytoma. The present study was designed to evaluate plasma and tissue NPY levels simultaneously as well as to study its release and expression in patients with either adrenal or extraadrenal pheochromocytomas. Plasma NPY levels were higher (P < 0.01) in patients with adrenal tumors than in matched normal subjects and patients with extraadrenal tumors. NPY levels were also higher (P < 0.05) in adrenal than in extraadrenal tumors. Bioactive NPY (1-36) was the predominant form in plasma and tumors of patients with adrenal pheochromocytomas. In contrast, patients with extraadrenal pheochromocytomas had an abundance of NPY fragments. NPY mRNA was abundant in 11 of 13 adrenal tumors but in only 1 of 6 extraadrenal tumors. Moreover, NPY was coreleased with NE with manipulation of adrenal but not extraadrenal tumors. These findings indicate that increased NPY gene expression in adrenal pheochromocytomas accounts for the greater biosynthesis and storage of NPY in these tumors and that increased release of NPY results in elevated plasma NPY. Factors regulating NPY gene expression in pheochromocytoma and the role of NPY in the clinical manifestations of the disease remain to be elucidated.
Colorectal cancer screening with fecal immunochemical testing had higher adherence than screening with guaiac-based FOBT
Authors: Harvey J. Murff
Journal: Annals of Internal Medicine (2010)

Source Citation Hoffman RM, Steel S, Yee EF, et al. Colorectal cancer screening adherence is higher with fecal immunochemical tests than guaiac-based fecal occult blood tests: a randomized, controlled trial. Prev Med. 2010;50:297-9. 20307568
Growth inhibition of human vascular smooth muscle cells by fenofibrate: a possible therapy for restenosis
Authors: E. Munro, M. Patel, P. Chan, L. Betteridge, K. Gallagher, M. Schachter, J. Wolfe, P. Sever
Journal: Cardiovascular Research (1994)

Objective: The aim was to assess the growth inhibitory effect of fibrates on human vascular smooth muscle cells. Restenosis is the most important factor limiting the long term success of invasive vascular interventions and there is as yet no effective preventive treatment. Platelet derived growth factor (PDGF) is considered to be an important growth promoting agent for vascular smooth muscle cells (VSMC) and fenofibric acid (a hypolipidaemic drug) has been reported to be a PDGF antagonist. Methods: The effect of the fibrate drugs fenofibrate, clofibrate, bezafibrate, and gemfibrozil were examined on the proliferation of cultured human vascular smooth muscle cells derived from saphenous vein (n = 20) and graft stenoses (n = 7). Results: Fenofibrate (100 μM) produced potent inhibition (48%) of VSMC proliferation at a concentration equivalent to that of its circulating metabolite fenofibric acid, but none of the other drugs produced any significant effect on growth. VSMC derived from graft stenoses were equally sensitive to inhibition as saphenous vein derived controls, in contrast to our previous work which reported that graft stenosis derived VSMC were resistant to growth inhibition by the physiological inhibitor heparin. The antiproliferative effect of fenofibrate was independent of inhibition of cellular cholesterol synthesis or toxicity. Fenofibrate inhibited VSMC growth induced by 15% fetal calf serum, PDGF, and basic fibroblast growth factor to a similar degree, indicating that it is not a specific PDGF antagonist. Conclusions: Fenofibrate is not a specific PDGF antagonist. Fenofibric acid, one of the principal metabolites of fenofibrate, did not produce any inhibition of growth, suggesting that oral administration of fenofibrate would not be efficacious. Fenofibrate is the first potent inhibitor to be described for VSMC derived from human myo-intimal hyperplastic lesions. Cardiovascular Research 1994;28:615-620
Three Thyrotoxic Criminals
Authors: PAUL J. DAVIS
Journal: Annals of Internal Medicine (1971)

Three young men without previous criminal records developed thyrotoxicosis and committed felonies while symptomatically hyperthyroid. In each case the loss, or threatened loss, of gainful employment was attributable to manifestations of thyrotoxicosis and was associated with the patients' reliance on larceny to support their dependents. There are no previous reports of the perpetration of criminal acts by symptomatic hyperthyroid patients. The legal defense of such patients may include consideration of hyperthyroidism as a mitigating factor.
Main-Stem Extrasystoles
Authors: HENRY J. L. MARRIOTT, SAMUEL M. BRADLEY
Journal: Circulation (1957)

Extrasystoles arising in the main stem of the bundle of His are generally regarded as very rare; only 7 examples have been published since their original description by Lewis in 1911 and 2 of these fail to satisfy rigid criteria for diagnosis. Four further examples, encountered in a relatively small series of tracings, are here presented and it is concluded that such extrasystoles are not so much rare as they are overlooked.
Clonal Conditional Mutagenesis in Malaria Parasites
Authors: Audrey Combe, Donatella Giovannini, Teresa Gil Carvalho, Stephan Spath, Bertrand Boisson, Céline Loussert, Sabine Thiberge, Céline Lacroix, Pascale Gueirard, Robert Ménard
Journal: Cell Host & Microbe (2009)