tbuckley/cabot-search huggingface dataset:
Abstract 5050: Biomarkers for sensitivity to gamma secretase inhibitors in mouse models of pancreatic adenocarcinoma
Authors: Arvind Dasari, Rebecca W. Powell, Lauren Puls, Kevin Quackenbush, Aik Choon Tan, Wells Messersmith, John Boylan, John Arcaroli
Journal: Cancer Research (2011)

Abstract Background: The Notch pathway is important in carcinogenesis and maintenance of pancreatic adenocarcinoma through its effects on cancer stem cells, cell differentiation and neoangiogenesis. RO4929097 is a novel oral inhibitor of the Notch pathway through its effects on γ-secretase, a key enzyme in this pathway. Several clinical trials are currently in progress with RO4929097 including a CTEP sponsored phase II trial in gemcitabine resistant metastatic pancreas cancer by our group. However, there are no biomarkers of sensitivity available currently for therapy with RO4929097 or other γ-secretase inhibitors (GSIs). Methods: We intend to treat 12 human pancreas cancer cell line mouse xenografts and 6 human primary pancreas tumor explants with RO4929097 (alone or in combination with gemcitabine) to identify sensitive (defined as tumors with ≥ 50% relative tumor growth inhibition with treatment) and resistant tumors. Subsequently, we propose to identify differences in gene expression by RT-PCR (Notch pathway), gene array or gene copy number by FISH between the resistant and sensitive tumors as potential biomarkers. Results: Of the eight pancreas cell line xenografts treated so far, four are sensitive to RO4929097. Comparison between sensitive and resistant tumors by gene array suggests that the sensitive cell lines exhibit higher levels of mesenchymal markers. In addition, two of the four human primary pancreatic explants treated thus far show intermediate sensitivity. RO4929097 in combination with gemcitabine in the four explants reveals a significant decrease in tumor growth inhibition for the combination compared to RO4929097 alone but the additive effect appears to be entirely due to gemcitabine. Similar effects were observed on tumor regrowth, upon observation after an initial period of treatment with either agents alone or in combination. In addition, future experiments to identify stem cell and/or angiogenesis specific biomarkers are also planned. Updated results will be presented at the meeting. Acknowledgements: This work was supported by Roche Pharmaceuticals Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 5050. doi:10.1158/1538-7445.AM2011-5050
Ondine's Kiss or Curse?
Authors: Duncan Topliss
Journal: JAMA (1981)

<h3>To the Editor.—</h3> The editorial by Samuel Vaisrub, MD (1981;245:1152), referred to my<i>Lancet</i>letter.<sup>1</sup>He seemed to have taken my whimsical suggestion that "Ondine's curse" be changed to "Ondine's kiss" rather too seriously; more important, he failed to appreciate that the version of the story of Ondine he described in the first paragraph has no literary foundation whatsoever, as the documentation of the origins of the story by Comroe<sup>2</sup>and Sugar (1978;240:236) have clearly shown. The story by de la Motte-Fouqué<sup>3</sup>is the original source for the eponym and not merely another version, although earlier references to ondines (water nymphs) certainly exist. Perhaps we should adopt Humpty-Dumpty's point of view—that words should mean just what we choose them to mean<sup>4</sup>—so that loss of respiratory automaticity may be described as Ondine's curse, while recognizing the literary error of this nomenclature. Current advances, however, in the
Softball sliding injuries. A prospective study comparing standard and modified bases
Authors: D. H. Janda
Journal: JAMA (1988)

In a previous retrospective study, base sliding was found to be responsible for 71% of recreational softball injuries. As most injuries occurred following rapid deceleration impact against stationary bases, quick-release (breakaway) bases were evaluated as a means to modify this mechanism of injury. Six hundred thirty-three softball games were played on breakaway-base fields and 627 games were played on stationary-base fields. Forty-five sliding injuries (7%) occurred on the stationary-base diamonds and only two sliding injuries (&lt;1%) occurred on the breakaway-base fields. Implementing the use of breakaway bases in recreational softball leagues could potentially achieve a significant, cost-effective reduction of injuries. (<i>JAMA</i>1988;259:1848-1850)
[731] IMPACT OF MODERATE ALCOHOL CONSUMPTION ON HEPATIC FIBROSIS PROGRESSION IN HCV-INFECTED PATIENTS
Authors: E. Marine Barjoan, E. Gelsi, P. Delasalle, N. Ibragimova, C. Sattonnet, M.C. Saint-Paul, C. Gueyffier, E. Diebolt, R. Hayek, J.G. Fuzibet, D. Ouzan
Journal: Journal of Hepatology (2007)
The novel Akt inhibitor, perifosine, induces caspase-dependent apoptosis and downregulates P-glycoprotein expression in multidrug-resistant human T-acute leukemia cells by a JNK-dependent mechanism
Authors: F Chiarini, M Del Sole, S Mongiorgi, G C Gaboardi, A Cappellini, I Mantovani, M Y Follo, J A McCubrey, A M Martelli
Journal: Leukemia (2008)
Nonspecific Medication Side Effects and the Nocebo Phenomenon
Authors: Arthur J. Barsky, Ralph Saintfort, Malcolm P. Rogers, Jonathan F. Borus
Journal: JAMA (2002)

Patients taking active medications frequently experience adverse, nonspecific side effects that are not a direct result of the specific pharmacological action of the drug. Although this phenomenon is common, distressing, and costly, it is rarely studied and poorly understood. The nocebo phenomenon, in which placebos produce adverse side effects, offers some insight into nonspecific side effect reporting. We performed a focused review of the literature, which identified several factors that appear to be associated with the nocebo phenomenon and/or reporting of nonspecific side effects while taking active medication: the patient's expectations of adverse effects at the outset of treatment; a process of conditioning in which the patient learns from prior experiences to associate medication-taking with somatic symptoms; certain psychological characteristics such as anxiety, depression, and the tendency to somatize; and situational and contextual factors. Physicians and other health care personnel can attempt to ameliorate nonspecific side effects to active medications by identifying in advance those patients most at risk for developing them and by using a collaborative relationship with the patient to explain and help the patient to understand and tolerate these bothersome but nonharmful symptoms.
REGRESSION OF CORONARY ATHEROMA VOLUME IN PATIENTS RECEIVING HIGH DOSE STATIN THERAPY: ANALYSIS OF THE SATURN STUDY
Authors: Stephen J. Nicholls, Christie Ballantyne, Phillip Barter, M. Chapman, Raimund Erbel, Peter Libby, Joel Raichlen, Kiyoko Uno, Rishi Puri, Yu Kataoka, Kathy Wolski, Steven Nissen
Journal: Journal of the American College of Cardiology (2012)
Primary health care in London--changes since the Acheson report.
Authors: B. Jarman, N. Bosanquet
Journal: BMJ (1992)

OBJECTIVE--To examine changes in primary care in London in the 11 years since the Acheson report on primary health care in inner London. DESIGN--Analysis of key data from the family health services authority performance indicators and from the Department of Health; study of trends since the time of the Acheson report; examination of the provision of primary care in 1990-1 and its relation to health and social factors. SETTING--Comparisons between the family health services authorities of inner London, outer London, and England as a whole, with a special study of Birmingham, Liverpool, and Manchester. SUBJECTS--The family health services authorities of England. RESULTS--There has been an improvement in the provision of primary care in inner London as judged by the criteria of the Acheson report, but these improvements have occurred only as part of an overall improvement in the provision of primary care in the country as a whole. None of the recommendations of the Acheson report specifically oriented to London have been implemented. There are some worrying trends in inner London, such as the increasing proportion of practices with more than 2500 patients. The problems faced by practitioners in inner London resemble those in other large inner city areas, but the primary care provision to deal with them is relatively poor.
MECHANICAL ILEUS COMPLICATING PREGNANCY
Authors: PHILIP SCHUYLER DOANE
Journal: JAMA (1910)

Mechanical obstruction, or ileus of the large or small intestine, is not infrequently encountered. Late diagnosis, together with imperfect technic, or late protracted operations, may be responsible for a high death-rate in all cases of this character. Refinement in diagnosis, with a perfected, rapid technic, will produce a marked reduction in this mortality. Naunyn reports a recovery of 75 per cent. of all patients with ileus operated on the first or second day of the attack, but the mortality was very great in all patients operated on the third day or later. This is verified by an analysis of cases reported during the past year as listed in the index. Very few cases are reported of ileus occurring during pregnancy. Williams reports two cases of intestinal obstruction complicating pregnancy. In one an intussusception occurred at the site of a tuberculous ulcer; the second was due to constriction by peritoneal adhesions
Plasma Levels and Therapeutic Effect of 25-Hydroxycholecalciferol in Epileptic Patients taking Anticonvulsant Drugs
Authors: T. C. B. Stamp, J. M. Round, D. J. F. Rowe, J. G. Haddad
Journal: BMJ (1972)

Plasma levels of 25-hydroxycholecalciferol (25-HCC) were measured by a specific competitive protein-binding assay. Mean levels in both normal London adults and adolescent schoolchildren were 16 ng/ml and the mean level in a group of epileptic patients on high-dosage anticonvulsant therapy was 5 ng/ml, (difference from normals P < 0.001). Two further epileptic patients, with well-marked anticonvulsant osteomalacia, were treated with small doses of 25-HCC during full metabolic balance studies; rapid healing followed administration of 25-HCC by mouth in doses of 10-45 mug daily, which is well below the effective dose range of calciferol in this condition. These findings provided further evidence that anticonvulsant osteomalacia results from hepatic enzyme induction which, by increasing the metabolism of cholecalciferol to inactive compounds, lowers 25-HCC levels in patients whose dietary vitamin D intake and exposure to sunlight are otherwise adequate. Results also indicated that under certain circumstances 25-HCC may have considerably stronger antirachitic potency in man than has hitherto been recognized.
Understanding Pathways of Calorie Restriction: A Way To Prevent Cancer?
Authors: K. Grifantini
Journal: JNCI Journal of the National Cancer Institute (2008)

F or decades, researchers have been intrigued by calorie restriction, a tried and true way of extending lifespans in creatures ranging from yeast and roundworms to flies and mice. Aside from increasing the lifespan of organisms up to 80% in some studies, calorie restriction (with proper nutrition) also leads to lower insulin, glucose, and blood pressure levels, as well as increased white blood cell count. Particularly enticing is the possibility for caloric restriction to prevent, delay, and shrink a variety of tumors, a fi nding that seems to complement those of recent studies linking obesity and cancer. In animal studies, researchers reduce food intake by 10% – 60%, but because such extreme dieting would be unrealistic in humans, many researchers are now examining the biological pathways affected by caloric restriction with the aim of developing preventive agents for cancer as well as other diseases associated with aging. Together with the growing fi eld of calorie restriction mimetics — fi nding natural or synthetic compounds that mimic the effects of caloric restriction — they are fi nding these pathways to be numerous and complex. “The fi eld of [caloric restriction] seems to grow every day with new discoveries of genes, pathways, and proteins that are affected in different ways,” Julie Mattison, Ph.D., a caloric restriction researcher at the National Institute on Aging (NIA), wrote in an e-mail. In gaining information about the systems changed by caloric restriction, she said, researchers can identify targets for mimetics.
Surgery for Small Cell Lung Cancer: A Retrospective Analysis of 243 Patients from Japanese Lung Cancer Registry in 2004
Authors: Hidefumi Takei, Haruhiko Kondo, Etsuo Miyaoka, Hisao Asamura, Ichiro Yoshino, Hiroshi Date, Meinoshin Okumura, Hirohito Tada, Yoshitaka Fujii, Yoichi Nakanishi, Kenji Eguchi, Hirotoshi Dosaka-Akita, Hideo Kobayashi, Noriyoshi Sawabata, Kohei Yokoi
Journal: Journal of Thoracic Oncology (2014)
Successful Treatment of Human Genital Herpes Infections With 2-Deoxy-D-glucose
Authors: Herbert A. Blough
Journal: JAMA (1979)

Thirty-six women with genital herpes infections (proved by virological or cytological means) were treated in a double-blind placebo-controlled study with the glucose analogue 2-deoxy-D-glucose for a three-week period. In initial mucocutaneous cases, 89% were cured, with two recurrences after 24 months; in the case of recurrent or secondary infections, 90% had a notable improvement manifested by no or less-frequent recurrences, fewer lesions, or shortened duration of symptoms. In initial infections, discomfort cleared within 12 to 72 hours of therapy; 90% of the patients were asymptomatic within four days. In both cases, virus shedding was notably reduced by 2-deoxy-D-glucose. Concomitant controls treated with placebos failed to respond within this time frame. The use of 2-deoxy-D-glucose provides a simple and unique approach to the treatment of genital herpesvirus infections. (<i>JAMA</i>241:2798-2801, 1979)
Chain of Friendship: Selected Letters of Dr. John Fothergill of London, 1735-1780
Authors: Lester S. King
Journal: JAMA (1971)

Dr. John Fothergill, prominent in the 18th century, is but little known to the 20th century. More's the pity! Into a family of influential Quakers, John was born in 1712, in Yorkshire. After a sound grammar school education he was apprenticed to an apothecary, but his ambition and abilities clearly marked him for higher professional status. As a dissenter he could not enter Oxford or Cambridge, but he did attend the medical school at the University of Edinburgh, which offered the best medical training available in Great Britain and from which he graduated in 1736. Fothergill rose rapidly to be one of the leading physicians in London. He also remained prominent in the affairs of the Quakers, and had very close ties with the Quaker colony of Pennsylvania. He knew all the leading men who visited England, and his counsels had considerable influence on Pennyslvania affairs. Botany comprised another of
The pathophysiology of acid-base changes in chronically phosphate-depleted rats: bone-kidney interactions.
Authors: M Emmett, S Goldfarb, Z S Agus, R G Narins
Journal: Journal of Clinical Investigation (1977)

Acid-base disturbances may develop secondary to the changes in renal tubular function and bone dynamics which attend phosphate depletion (PD). This work characterizes the acid-base status of rats fed a low phosphate diet. After 18 days, PD rats had marked calciuria (pair-fed controls: 0.3 +/- 0.2; PD 32.2 +/- 2.5 mueq/h; P less than 0.001), severe bicarbonaturia (controls: 0; PD 17.6 +/- 0.2 meq/h; P less than 0.001), and negative net acid excretion (controls: 44.5 +/- 2.9; PD: --6.6 +/- 2.5 meq/h; P less than 0.001), but plasma pH, HCO3, and PCO2 were equal in both groups. After 45 days, plasma HCO3 fell to 21.1 +/- 0.9 meq/liter in PD (controls: 23.6 +/- 0.5 meq/liter; P less than 0.05), while bicarbonaturia (controls: 0.4 +/- 0.2; PD: 3.8 +/- 1 mueq/h; P less than 0.02) and calciuria were present but diminished. These data suggested the coexistence of bone HCO3 mobilization and renal HCO3 wasting in PD. To test this thesis, bicarbonaturia was eliminated by nephrectomy. 24 h later plasma HCO3 was higher in PD rats (controls: 19.3 +/- 0.02; PD: 22.6 +/- 0.8 meq/liter; P less than 0.05), consistend with the presence of extrarenal HCO3 production. After inhibition of bone resorption with colchicine (1 mg/kg), plasma HCO3 decreased to 16.8 +/- 0.6 meq/liter in PD rats (controls): 26.4 +/- 1 meq/liter; P less than 0.001) while bicarbonaturia persisted. These data indicate that the plasma HCO3 in PD is the net result of renal HCO3 wasting and bone HCO3 mobilization. These combined effects maintain normal blood HCO3 initially (18 days) but with time (45 days), bone resorption diminishes and the acidifying renal tubular defect predominates.
Substitution rates of organelle and nuclear genes in sharks: implicating metabolic rate (again)
Authors: A. P. Martin
Journal: Molecular Biology and Evolution (1999)

Rates of nucleotide substitution for nuclear genes are thought to be governed primarily by the number of germ line replication events (the so-called "generation time" hypothesis). In contrast, rates of mitochondrial DNA evolution appear to be set primarily by DNA damage pathways of mutation mediated by mutagenic by-products of oxidative phosphorylation (the so-called "metabolic-rate" hypothesis). Comparison of synonymous substitution rates estimated for the mitochondrial cytochrome b gene and nuclear-encoded dlx, hsp70, and RAG-1 genes in mammals and sharks shows that rates of molecular evolution for sharks are approximately an order of magnitude slower than those for mammals for both nuclear and mitochondrial genes. In addition, there is significant positive covariation of substitution rate for mitochondrial and nuclear genes within sharks. These results, interpreted in light of the pervasiveness of DNA damage by mutagenic by-products of oxygen metabolism to both nuclear and mitochondrial genes and coupled with increasing evidence for cross-genome activity of DNA repair enzymes, suggest that molecular clocks for mitochondrial and nuclear genes may be set primarily by common mutational mechanisms.
Lin28 promotes transformation and is associated with advanced human malignancies
Authors: Srinivas R Viswanathan, John T Powers, William Einhorn, Yujin Hoshida, Tony L Ng, Sara Toffanin, Maureen O'Sullivan, Jun Lu, Letha A Phillips, Victoria L Lockhart, Samar P Shah, Pradeep S Tanwar, Craig H Mermel, Rameen Beroukhim, Mohammad Azam, Jose Teixeira, Matthew Meyerson, Timothy P Hughes, Josep M Llovet, Jerald Radich, Charles G Mullighan, Todd R Golub, Poul H Sorensen, George Q Daley
Journal: Nature Genetics (2009)
Idiopathic Acute Esophageal Necrosis: Not Necessarily a Terminal Event
Authors: M. Moretó, E. Ojembarrena, M. Zaballa, J. G. Tánago, S. Ibáǹez
Journal: Endoscopy (1993)

See also: Idiopathic Acute Esophageal Necrosis: Report of a New CaseEndoscopy 1994; 26(08): 713-713DOI: 10.1055/s-2007-1009078
I just wanted to be a doctor: Medicine and its representation
Authors: P. G Davies
Journal: BMJ (2006)

I just wanted to be a doctorWe need to be more than "just" doctors Editor-Hunt articulates the feelings of many doctors on discovering that the effective practice of modern medicine requires a range of skills beyond the provision of direct clinical care. 1 Her slightly delayed entry into medicine may explain why this issue is troubling her now, rather than later in her career: certainly these are sentiments I hear more commonly from consultant colleagues than juniors.However, to imagine that good medical practice is confined to the delivery of care to one patient at a time is to overlook the role of doctors in organising healthcare systems and delivery in the wider context.It is disappointing that Hunt's appraiser chose to frame the process in terms of her trust's participation in the clinical negligence scheme, since most junior doctors value well conducted appraisals.Nevertheless, cheaper insurance premiums for hospitals mean more money to spend on health care, and also indicate that organisations that carry out effective appraisal make fewer clinical errors: presumably these are both outcomes that Hunt would approve of.Furthermore, research and audit without the active participation of doctors will soon become clinically irrelevant or ineffective.We have a wider responsibility for patient care that is served by informed participation in these and many other activities, such as teaching and continuous quality improvement (which also seem to get irritatingly in the way of a narrowly focused approach to patient care).However, all is not lost.Hunt appears well placed to fall into the "Modernising Medical Careers" vacuum that currently threatens to swallow those junior doctors who are too old for a foundation programme yet too young to have secured a specialist registrar post.If this does indeed curtail all opportunities for career progression she may end up as "just" a doctor after all.
Gene expression profiling distinguishes JAK2V617F-negative from JAK2V617F-positive patients in essential thrombocythemia
Authors: E Puigdecanet, B Espinet, J J Lozano, L Sumoy, B Bellosillo, L Arenillas, A Álvarez-Larrán, F Solé, S Serrano, C Besses, L Florensa
Journal: Leukemia (2008)
Drug Delivery: Platinum (IV) Pro‐Drug Conjugated NaYF<sub>4</sub>:Yb<sup>3+</sup>/Er<sup>3+</sup> Nanoparticles for Targeted Drug Delivery and Up‐Conversion Cell Imaging (Adv. Healthcare Mater. 4/2013)
Authors: Yunlu Dai, Xiaojiao Kang, Dongmei Yang, Xuejiao Li, Xiao Zhang, Chunxia Li, Zhiyao Hou, Ziyong Cheng, Ping'an Ma, Jun Lin
Journal: Advanced Healthcare Materials (2013)

A folic acid targeted anticancer drug delivery system based on Pt (IV) complexes pro-drug conjugated upconversion NaYF4:Yb3+/Er3+ nanoparticles is developed. As reported by Jun Lin, Ping'an Ma, and co-workers on page 562, the platinum (IV) complexes as pro-drugs can exhibit anti-cancer activities when the platinum (IV) complexes are reduced to platinum (II) in the intracellular environment. The nanoparticles show bright upconversion fluorescence under 980 nm laser excitation; thus, the as-prepared nanoparticles can be used as a luminescent probe for up-conversion cell imaging.
HSV-Mediated Delivery of Erythropoietin Restores Dopaminergic Function in MPTP-Treated Mice
Authors: Veljko Puskovic, Darren Wolfe, James Wechuck, David Krisky, Jeff Collins, Joseph C. Glorioso, David J. Fink, Marina Mata
Journal: Molecular Therapy (2006)

To investigate the neuroprotective effects of erythropoietin (EPO) in a rodent model of Parkinson disease, we inoculated a nonreplicating herpes simplex virus-based vector expressing EPO (vector DHEPO) into the striatum of mice 1 week prior to, or 2 weeks after, the start of continual administration of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) (4 mg/kg intraperitoneally, 5 of 7 days) for 6 weeks. Inoculation with DHEPO prior to MPTP intoxication preserved behavioral function measured by pellet retrieval and the histological markers of tyrosine hydroxylase-immunoreactive (TH-IR) neuronal cell bodies in the substantia nigra (SN) and TH-IR and dopamine transporter-immunoreactive (DAT-IR) terminals in striatum. Inoculation of DHEPO 2 weeks into a 6-week course of MPTP resulted in improvement of behavioral function and restoration of TH-IR cells in SN and TH- and DAT-IR in the striatum. The effects of vector-produced EPO were similar in magnitude to the effects of vector-mediated expression of glial-derived neurotrophic factor in the same model. These results demonstrate that vector-mediated EPO production may be used to reverse dopaminergic neurodegeneration in the face of continued toxic insult.