tbuckley/cabot-search huggingface dataset:
Abstract 3358: Significant increase in survival of triple negative breast cancer animal model in response to BPM31510 alone or in combination with standard of care: BPM31510 mediated dynamic metabolic (Warburg) shift in breast cancer as potential mechanism
Authors: Niven R. Narain, Anne R. Diers, Tony E. Walshe, Arleide Lee, Rakib Ouro-Djobo, Vivek K. Vishnudas, Ely Benaim, Rangaprasad Sarangarajan
Journal: Cancer Research (2014)

Abstract This study demonstrates that BPM 31510, a Coenzyme Q10 containing proprietary formulation to influences cellular metabolism that is deregulated in cancers and is now considered to be a “hallmark of cancer”. These studies demonstrate that BPM 31510 alone or in combination with standard of care significantly improved survival of triple negative breast cancer (TNBC) animal model. To further tease out beneficial effects of BPM31510, human breast cancer cells of varying receptor status (SKBR3, MDA-MB231) were subjected to either (a) pretreatment with BPM 31510 (6 h) followed co-incubation with chemotherapeutic agents for 48-72 h or (b) co-treatment with BPM 31510 and chemotherapeutic agents, and cancer cell responses were compared to non-tumorigenic mammary cells (MCF12A). Cellular bioenergetics profiling revealed that BPM 31510 shifted cellular metabolism from glycolysis to mitochondrial metabolism, and this metabolic shift was associated with significant increases in reactive oxygen species (ROS). Both BPM 31510 alone or pretreatment and cotreatment strategies with BPM 31510 plus standard of care resulted in significant decreases in viable breast cancer cells when compared to chemotherapeutic agents; however, minimal effects were observed in MCF12A cells. In contrast, BPM 31510 in combination with chemotherapeutic agents amplified caspase 3 activation and apoptotic cell death, indicating BPM 31510 enhances apoptotic signaling. Taken together, these data demonstrate that BPM 31510 is a novel agent that reengages the cellular metabolic and apoptotic machinery of cancer cells independent of genetic make-up underlying malignancy. In addition, BPM 31510 enhances the cytotoxicity of standard-of-care chemotherapeutic agents in breast cancer cells through regulation of mitochondrial metabolism and oxidative stress. These findings confirm that BPM 31510 is a novel, paradigm shifting agent with multiple utility (as a single agent or in combination) in breast cancer including TNBCs that otherwise have poor prognosis and limited therapeutic options. Citation Format: Niven R. Narain, Anne R. Diers, Tony E. Walshe, Arleide Lee, Rakib Ouro-Djobo, Vivek K. Vishnudas, Ely Benaim, Rangaprasad Sarangarajan. Significant increase in survival of triple negative breast cancer animal model in response to BPM31510 alone or in combination with standard of care: BPM31510 mediated dynamic metabolic (Warburg) shift in breast cancer as potential mechanism. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 3358. doi:10.1158/1538-7445.AM2014-3358
Synchronicity and its use in the brain
Authors: Guenther Palm, Thomas Wennekers
Journal: Behavioral and Brain Sciences (1997)

We briefly review the long-standing ideas about the use of synchronicity in the brain, which rely on Donald Hebb's views on cell assemblies and synaptic plasticity. More recently the distinction among several timescales in the description of neural activity has become a focus of theoretical discussion. Phillips &amp; Singer's target article is criticized mainly because it does not distinguish these timescales properly and hence does not really address the questions so intensely debated today.
Mite allergens: significance of enzymatic activity
Authors: C. R. A. Hewitt, S. Foster, C. Phillips, H. Horton, R. M. Jones, A. P. Brown, B. J. Hart, D. I. Pritchard
Journal: Allergy (1998)

Ten years ago, the cloning and sequencing of a cDNA encoding the group I allergen of house‐dust mites unequivocally determined that protein allergens may have biochemical functions in addition to their ability to bind IgE. Since this discovery, several groups have speculated that the biochemical activities of allergens, or substances associated with allergens, may be involved in their immunogenicity or allergenicity. This paper will focus on just one biochemical function, proteolytic activity, and will be illustrated by examples of our own work that we believe support the hypothesis that this category of molecules are endowed with the properties of proallergic adjuvants.
A Pilot Study of All-<i>trans</i>-Retinoic Acid for the Treatment of Human Emphysema
Authors: JENNY T. MAO, JONATHAN G. GOLDIN, JOHN DERMAND, GRACE IBRAHIM, MATHEW S. BROWN, ALETHA EMERICK, MICHAEL F. McNITT-GRAY, DAVID W. GJERTSON, FRANCINE ESTRADA, DONALD P. TASHKIN, MICHAEL D. ROTH
Journal: American Journal of Respiratory and Critical Care Medicine (2002)

Emphysema results from progressive destruction of alveolar septae and was considered irreversible until all-trans-retinoic acid (ATRA) was shown to reverse anatomic and physiologic signs of emphysema in a rat model. To evaluate the feasibility of ATRA as a clinical therapy, 20 patients with severe emphysema were enrolled into a randomized, double-blind, placebo-controlled pilot study. Participants included 16 male and 4 female former smokers, two with α1-antitrypsin deficiency. Patients were treated with either 3 mo of ATRA (50 mg/m2/d) or 3 mo of placebo, followed by a 3-mo crossover phase. Plasma drug levels were followed and outcome measures included serial pulmonary function tests, blood gases, lung compliance, computed tomography (CT) imaging, and quality of life questionnaires. In general, treatment was well tolerated and associated with only mild side effects including skin changes, transient headache, hyperlipidemia, transaminites, and musculoskeletal pains. Plasma drug levels varied considerably between subjects and decreased significantly over time in 35% of the participants. Physiologic and CT measurements did not change appreciably in response to therapy. We conclude that ATRA is well tolerated in patients with emphysema, and trials evaluating higher doses, longer treatment, or different dosing schedules are feasible.
Mortality in Middle-Aged Smokers and Nonsmokers
Authors: Gary D. Friedman, Loring G. Dales, Hans K. Ury
Journal: New England Journal of Medicine (1979)

We assessed the relation of cigarette smoking to mortality in an 11-year follow-up study of 4004 men and women, 35 to 54 years of age, who responded to urging to have multiphasic health checkups. Accounting for 48 other characteristics, both individually and in combination, failed to eliminate the association of smoking with mortality from all causes or with mortality from coronary heart disease. The smoker-to-nonsmoker mortality ratios, crude and adjusted respectively, were 2.6 and 2.1 for all causes and 4.7 and 3.6 for coronary heart disease. This analysis did not support the counterhypothesis that the association of cigarette smoking with mortality is secondary to some underlying characteristic. (N Engl J Med 300:213–217, 1979)
Of Mugs and Marketing
Authors: Larry R. Kirkland
Journal: JAMA (1991)

<h3>To the Editor.</h3> — In their my-shirt-has-more - hair - in - it - than - yours - does exchange over advertising in medical journals, neither Dr Goldstein<sup>1</sup>nor Dr Rennie<sup>2</sup>mentioned what I always considered a reasonable compromise. To wit, put the advertisements en bloc before and after the substantive text, as is done in the<i>New England Journal of Medicine</i>. Advertising revenue is retained and those "readers [who] keep telling editors that they find the ads informative"<sup>2</sup>know where they are. On the other hand, readers who object to the advertisements can tear 'em out without a glance. Rennie may decry "the throwaway journals... being merely the inventions and creatures of the advertising industry," but<i>JAMA</i>'s present interspersion of advertisements is only marginally better than most of the throwaways.
Health information for the developing world
Authors: R Kale
Journal: BMJ (1994)

Doctors and other health professionals in developing countries are missing out on relevant information about health. A lot of the information they need is available in the developed countries, and those who have it are happy to share it with them. But transporting information, like food or medicines, from one part of the world to another is not an easy task nor is it the complete answer to the information drought. It is one thing to ferry books and journals from Europe to Africa and another to make relevant information available to the right person at the right time at an affordable cost.Gross inequalities exist in the availability of health information in the developing and developed worlds. While doctors in developed countries receive more information than they can possibly absorb and use, doctors and other health professionals in most developing countries suffer from an extreme shortage of relevant information. This paucity of relevant information is a chronic problem of health care in developing countries and in the formerly communist countries of eastern Europe. A conference was held in 1994 at the BMA House, London, to bring together people who know what material is wanted in developing countries, publishers who might make health material available as cheaply as possible, and people who know about distributing it to the developing world. A network of concerned individuals is now being established among some of the 67 conference participants who included representatives of international organizations, government and nongovernment bodies, as well as publishers, journalists, doctors, and others. The conference also helped highlight the need for certain health-related information to be generated in and by developing countries and that the information exchange should be from developed countries to developing countries, vice versa, and among developing countries. The author explains information needs, present action, the role of international organizations, what librarians can do, problems faced by commercial publishers, how the distribution of information can be improved, the role of electronic publishing and distribution, and how publishers in developing countries can be helped.
Clinical Experience and Evidence-Based Medicine
Authors: Robert G. Badgett
Journal: Annals of Internal Medicine (1998)

Letters1 February 1998Clinical Experience and Evidence-Based MedicineRobert G. Badgett, MD, Mary O'Keefe, MD, and Mark C. Henderson, MDRobert G. Badgett, MDThe University of Texas Health Science Center at San Antonio; Audie L. Murphy Veterans Administration Hospital; San Antonio, TX 78284Search for more papers by this author, Mary O'Keefe, MDThe University of Texas Health Science Center at San Antonio; Audie L. Murphy Veterans Administration Hospital; San Antonio, TX 78284Search for more papers by this author, and Mark C. Henderson, MDThe University of Texas Health Science Center at San Antonio; Audie L. Murphy Veterans Administration Hospital; San Antonio, TX 78284Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-128-3-199802010-00020 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail IN RESPONSE:We completely agree that clinical experience is critical to decision making and teaching. As we stated in our abstract and paper, systematic reviews are meant not to replace clinician decision making but rather to enhance it.We avoided stating precisely how much medical decision making should be based on systematic reviews and medical evidence as opposed to clinical experience. However, on the basis of the observation that recommendations of expert clinicians frequently contradict published medical evidence [1], we believe that many physicians rely excessively on clinical experience. Clinical experience is essential but should be complemented by evidence-based medicine ...References1. Antman EM, Lau J, Kupelnick B, Mosteller F, Chalmers TC. A comparison of results of meta-analyses of randomized control trials and recommendations of clinical experts. Treatments for myocardial infarction. JAMA. 1992; 268:240-8. Google Scholar Author, Article, and Disclosure InformationAffiliations: The University of Texas Health Science Center at San Antonio; Audie L. Murphy Veterans Administration Hospital; San Antonio, TX 78284 PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 February 1998Volume 128, Issue 3Page: 245KeywordsDecision makingEvidence based medicinePatientsSystematic reviews Issue Published: 1 February 1998 CopyrightCopyright © 1998 by American College of Physicians. All Rights Reserved.PDF DownloadLoading ...
Incremental Coverage of the Uninsured
Authors: Karen Davis
Journal: JAMA (1996)

Trends in today's health care marketplace are putting care for the uninsured at risk. The numbers of insured are growing,<sup>1</sup>and safety net providers such as public hospitals and community health centers are feeling the financial strain of the growth of Medicaid managed care. The uninsured have experienced difficulty obtaining needed care in the past,<sup>2-7</sup>and their ability to obtain such care in the future is in even greater jeopardy. In the absence of attention to the aggregate problem of the uninsured, special focus on vulnerable subpopulations—Children, low-income women, the unemployed, and older uninsured adults—should receive greatest priority. Incremental changes that would expand health insurance coverage to groups most likely to benefit from access to care would reduce the immediate burdens created by shrinking availability of free care. <h3>Incremental Options for Expanding Health Insurance Coverage</h3> Building on existing programs and administrative structures offers a foundation for incremental expansions.
1128 Effect of alcohol consumption on CYP2E1 and CYP3A activities in humans: insight into acetaminophen hepatotoxicity in alcoholics
Authors: S LIANGPUNSAKUL, C GORSKI, D CRABB, S HALL, N CHALASANI
Journal: Hepatology (2003)

While methamphetamine (MA) and alcohol are often used in combination, little is known about the pattern of co-use between these substances. The goal of the present study is to examine the relationship between MA use and alcohol use in a community sample of non-treatment seeking regular MA users.Participants completed a face-to-face assessment battery, which included a diagnostic interview for MA dependence and the timeline follow-back interview for both alcohol and MA use over the past 30 days. Sixty regular MA and alcohol users supplied data for 1800 person-days.Compared with non-drinking days, drinking days and binge drinking days increased the odds of same day MA use by 4.22 and 4.50 times, respectively (p's < 0.0001). Further, binge drinking incrementally increased risk for MA use above and beyond the effects of drinking itself (p < 0.0001). Lagged models revealed previous day MA use to predict following day MA use (p < 0.0001), yet, after controlling for this relationship, neither previous day alcohol use nor previous day binge drinking predicted following-day MA use. Finally, the effect of binge drinking on MA use was stronger among individuals with lower MA dependence severity or higher alcohol problem severity (p's < 0.05).These results suggest that alcohol and MA are co-used in predictable patterns, and in particular, that binge drinking may be incrementally associated with the likelihood of MA use. Future studies are needed to explore the temporal relationship between alcohol and MA use within a given episode.
Phenotypical heterogeneity of CD4+CD8+ double-positive chronic T lymphoid leukemia
Authors: M Mizuki, S Tagawa, T Machii, M Shibano, E Tatsumi, K Tsubaki, H Tako, A Yokohama, S Satou, J Nojima, T Hirota, T Kitani
Journal: Leukemia (1998)
Effective Management and the Future of the NHS
Authors: John Lister
Journal: New England Journal of Medicine (1971)

THE future of the National Health Service (NHS) has been discussed with almost monotonous regularity since its inception in 1948. It has been subjected to criticism at times by patients and doctors alike, whereas politicians have often regarded it with an apparent euphoria and protested that it has been the envy of the world. Although it has shown signs of foundering because of inadequate finance, most politicians have been afraid to introduce any important direct charges that might suggest that they were interfering with the fundamental principle that its facilities should at any rate appear to be free at the . . .
Diagnostic Value of Contrast-Enhanced Magnetic Resonance Imaging and Single-Photon Emission Computed Tomography for Detection of Myocardial Necrosis Early After Acute Myocardial Infarction
Authors: Tareq Ibrahim, Hubertus P. Bülow, Thomas Hackl, Mira Hörnke, Stephan G. Nekolla, Martin Breuer, Albert Schömig, Markus Schwaiger
Journal: Journal of the American College of Cardiology (2006)
Choice is a gift from the patient to the doctor, not the other way around
Authors: A. Harrison
Journal: BMJ (2000)

EDITOR—I agree with Taylor that many patients are happy to let their doctor have the ultimate decision about treatment, and rightly so, based on their doctor's years of training and experience.1 This may especially be the case in Taylor's highly technical specialty, anaesthesia. All that most patients want of their anaesthesia is not to feel any pain and to still be alive …
Post tropical screening. ...unless the traveller feels unwell.
Authors: C J Ellis
Journal: BMJ (1993)

matory drugs may exert tumoricidal effects in the colon,4 thus accounting for the reduced risk of cancer of the colon with regular use of these drugs.Large scale therapeutic trials of non-steroidal antiinflammatory drugs in established cancers of the colon and chemopreventive trials in high risk patients would therefore be appropriate since the risk of potential side effects in such cohorts would be justified.Initial reports of such studies are encouraging.5
Steroid Receptors and Hormone Receptivity
Authors: Etienne-Emile Baulieu
Journal: JAMA (1975)

HORMONES are informational molecules. These chemical messengers must find, in the target cells, specific recognition mechanisms that will select them appropriately from all other components of the "milieu intérieur." These recognition mechanisms, which involve binding sites (r on Fig 1) of very high affinity (dissociation constant, K<sub>D</sub>, between 0.1 and 10 nanomolar [nM], adjusted to the low concentration of hormones in the plasma) and strict (stereo) specificity, constitute the primary function of receptors. We know that the catalytic sites of enzymes also display specificity, but the affinity is 10<sup>4</sup>times lower than that of the hormone-receptor binding sites, since substrates such as sugars, amino acids, or lipids are found there in higher concentration and then transformed into products. In contrast, the interaction of hormones with their receptors does not alter their chemical composition per se; it is a purely "physical" phenomenon. <h3>Receptors</h3> The capacity for specific binding, even
THE EFFECT OF LOCAL TEMPERATURE VARIATIONS ON THE SEBUM EXCRETION RATE
Authors: W. J. CUNLIFFE, J. L. BURTON, SAM SHUSTER
Journal: British Journal of Dermatology (1970)

SUMMARY.– The effect of a local increase or decrease in skin temperature on the rate of sebum excretion from forehead skin was studied in 9 subjects. The relationship between skin temperature and sebum excretion rate was highly significant, and heating and cooling produced changes of the orders of 10% per 1°C. These changes occurred within 90 min., which suggests that the sebum excretion rate measured by the present technique may not always accurately reflect the rate of sebum production deep in the glands. Variations in temperature affect the rate at which sebum is absorbed by the collecting papers, probably due to changes in sebum viscosity, and this could explain the observed changes in sebum excretion.
1025 THE COG 2 GENE A2217G SINGLR NUCLEOTIDE POLYMORPHISM CONFERS SUSCEPTIBILITY TO HEPATOCYTE BALLOONING IN NASH PATIENTS
Authors: T. Saibara, T. Ochi, G. Munekage, K. Ogasawara, A. Hirose, Y. Nozaki, M. Takahashi, M. Ono, M. Morita
Journal: Journal of Hepatology (2009)
Cost of Medical Care
Authors: James Scott
Journal: JAMA (1979)

<h3>To the Editor.—</h3> The article "Outcome and Cost for Stroke Patients in Academic and Community Hospitals: Comparison of Two Groups Referred to a Regional Rehabilitation Center (240:1878,1978) is a welcome addition to accumulating studies suggesting that the overspecialized and overmechanized medicine in supercenters is not necessarily beneficial to the patient and is always expensive. We also receive similar reports about the overdiagnosis and overtreatment in our costly intensive care units. Since the cost factor will be dominant in the medicine of coming years, the pendulum must swing in the opposite direction. The downgraded community hospital and the humble family physician must regain their old recognition.
Nonsteroidal Anti-inflammatory Agents in Rheumatoid Arthritis and Ankylosing Spondylitis
Authors: Cody Wasner
Journal: JAMA (1981)

The relative effectiveness of six nonsteroidal anti-inflammatory agents was studied in 33 patients with rheumatoid arthritis and 32 patients with ankylosing spondylitis in a double-blind, randomized, prospective study employing a six-way multiple crossover design with six-week trials of each agent. In ankylosing spondylitis, naproxen, indomethacin, and fenoprofen calcium were the most effective agents. In rheumatoid arthritis, relatively little mean difference between drugs was found. Most of this difference could be attributed to compliance factors, which favored drugs that required only a small number of pills daily. Despite the small differences in effect, patients had strong preferences. More than 85% of patients were still taking their preferred medication after a mean follow-up period of one year.
THE NUMERICAL LAWS GOVERNING THE RATE OF EXCRETION OF UREA AND CHLORIDES IN MAN
Authors: Franklin C. McLean
Journal: The Journal of Experimental Medicine (1915)

1. The excretion of urea and of chlorides in the normal individual is carried out according to definite laws, capable of numerical expression. 2. The rate of excretion of urea and of sodium chloride is determined by the concentration in the blood, the rate of water output, and indirectly by the weight of the individual. 3. The threshold of sodium chloride excretion is practically constant at about 5.62 grams of sodium chloride per liter of plasma. Slight variations in the threshold occur in normal individuals. 4. The rate of excretion of urea under the conditions found at any time can be measured directly in terms of the normal by an index of urea excretion.
USE OF THE SINGLE CELL METHOD IN OBTAINING PURE CULTURES OF ANAEROBES
Authors: M. A. Barber
Journal: The Journal of Experimental Medicine (1920)

The pipette method has proved a feasible method of obtaining one-cell pure cultures of anaerobes. Both bacilli and spores may be used as seeding material, but spores give a much higher percentage of positives. Boiling alone affords a sufficient degree of anaerobiosis to the medium for initiating one-cell growths, and semisolid agar is the most convenient form of medium. Exposure to air during isolation apparently has no effect on the viability of spores of anaerobes, but young bacilli of some species suffer from a comparatively short exposure to free oxygen.
REDUCTION IN PULMONARY ADVERSE EVENTS AND ASSOCIATED SEPSIS AND MORTALITY IN ACUTE CORONARY SYNDROME PATIENTS TREATED WITH TICAGRELOR COMPARED TO CLOPIDOGREL: A POST HOC ANALYSIS OF THE PLATO STUDY
Authors: Robert F. Storey, Philippe Steg, Stefan James, Steen Husted, Christopher Cannon, Richard Becker, Joseph Ycas, Nils &Aring;senblad, Jan Kilhamn, Lars Wallentin
Journal: Journal of the American College of Cardiology (2012)