tbuckley/cabot-search huggingface dataset:
Abstract 2951: Vitamin C is selectively toxic to cancer cells harboring KRAS or BRAF mutations by targeting GAPDH
Authors: Jihye Yun, Adam Kavalier, Edouard Mullarky, Kaitlyn Bosch, Jatin Roper, Carlo Rago, Jihye Paik, John Asara, Steven Gross, Bert Vogelstein, Nickolas Papadopoulos, Lewis Cantley
Journal: Cancer Research (2014)

Abstract Although more than half of colorectal cancer patients have either KRAS or BRAF mutations, targeted therapies for these subgroups of cancer patients are still lacking. Here, we report that KRAS or BRAF mutant cells exhibit a significant increase in the uptake of oxidized vitamin C, dehydroascorbate (DHA), via the GLUT1 glucose transporter. Increased uptake of DHA in the mutant cell lines causes oxidative stress as intracellular DHA is immediately reduced back to vitamin C by reduced glutathione. Elevated reactive oxygen species inactivate GAPDH and thus divert glycolytic flux into the pentose phosphate pathway. Because KRAS or BRAF mutant cells are highly dependent on glycolysis, this altered glucose metabolism induced by vitamin C ultimately leads to an energy deficit in KRAS or BRAF mutant cells and thereby cell death. There are currently a growing number of clinical trials in phases I/II examining the effect of high dose vitamin C as a treatment for cancers, including colorectal cancers. Our results provide a rationale for the pharmacological use of vitamin C as a therapeutic agent to treat colorectal cancer patients with oncogenic KRAS or BRAF mutations. Citation Format: Jihye Yun, Adam Kavalier, Edouard Mullarky, Kaitlyn Bosch, Jatin Roper, Carlo Rago, Jihye Paik, John Asara, Steven Gross, Bert Vogelstein, Nickolas Papadopoulos, Lewis Cantley. Vitamin C is selectively toxic to cancer cells harboring KRAS or BRAF mutations by targeting GAPDH. [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 2951. doi:10.1158/1538-7445.AM2014-2951
Elevated Blood Lead Concentrations and Vitamin D Deficiency in Winter and Summer in Young Urban Children
Authors: Francis W. Kemp, Prasad V.S.V. Neti, Roger W. Howell, Peter Wenger, Donald B. Louria, John D. Bogden
Journal: Environmental Health Perspectives (2006)

It is widely recognized that blood lead concentrations are higher in the summer than in winter. Although the effects of some environmental factors such as lead in dust on this phenomenon have been studied, relationships to sunlight-induced vitamin D synthesis have not been adequately investigated. Vitamin D status is influenced by the diet, sunlight exposure, age, skin pigmentation, and other factors, and may modify gastrointestinal lead absorption or release of lead stored in bones into the bloodstream.We collected paired blood samples from 142 young, urban African-American and Hispanic children in the winter and summer to study the seasonal increase in blood lead and its relationships to vitamin D nutrition, age, and race.A winter/summer (W/S) increase in blood lead concentrations of 32.4% was found for children 1-3 years of age. There was a smaller W/S increase of 13.0% in children 4-8 years of age. None of the 51 Hispanic children had an elevated blood lead concentration (> or = 10 microg/dL) during the winter, and only one had an elevated summertime concentration. In contrast, elevated blood lead concentrations were frequent in the 91 African-American children, especially those 1-3 years of age. For the latter, the percentage with elevated blood lead levels increased from 12.2% in winter to 22.5% in summer. A 1.2% W/S increase in serum 25-hydroxy-vitamin D (serum 25-OH-D) concentrations was found for children 1-3 years of age. However, in children 4-8 years of age the W/S increase in serum 25-OH-D was much larger-33.6%. The percentages of children with low (< 16 microg/L) serum 25-OH-D concentrations were 12.0% in winter and 0.7% in summer and were consistently greater in African-American than in Hispanic children. The seasonal increases in blood lead and serum 25-OH-D in children 4-8 years of age were significantly associated.The higher summertime serum 25-OH-D concentrations for the 4- to 8-year-old children are likely caused by increased sunlight-induced vitamin D synthesis and may contribute to the seasonal increase in blood lead. Age and race are key factors that affect blood lead and vitamin D nutrition, as well as their interactions, in young urban children.
Sensorineural Deafness and Seizures in Mice Lacking Vesicular Glutamate Transporter 3
Authors: Rebecca P. Seal, Omar Akil, Eunyoung Yi, Christopher M. Weber, Lisa Grant, Jong Yoo, Amanda Clause, Karl Kandler, Jeffrey L. Noebels, Elisabeth Glowatzki, Lawrence R. Lustig, Robert H. Edwards
Journal: Neuron (2008)
Use of Krypton <sup>85</sup> for the Measurement of Cardiac Output by the Single-Injection Indicator-Dilution Technique
Authors: WILLIAM P. CORNELL, EUGENE BRAUNWALD, EDWIN C. BROCKENBROUGH
Journal: Circulation Research (1961)

When krypton 85 in saline solution is injected into the left side of the heart and sampled from a systemic artery, or is injected into a peripheral vein and sampled from the pulmonary artery, only the primary time-concentration curve is obtained. Recirculation is eliminated by the diffusion of this indicator into the extravascular space and its loss from the pulmonary capillary bed. Determination of the radioactivity in a single blood sample, withdrawn at a constant rate throughout the period during which the Kr 85 passes across. the sampling site, permits calculation of the average concentration of Kr 85 during the inscription of the primary curve. The validity of this technique was tested in a circulatory model against actual flow determined by timed collection. One standard deviation of the differences in 27 trials equaled 5.1 per cent. In 26 comparisons of cardiac output determined simultaneously in dogs by a rotameter and the Kr 85 technique, one standard deviation of the differences equaled 8.4 per cent. In 19 comparisons of cardiac output in patients, determined by dye-dilution and Kr 85 techniques, one standard deviation of the differences equaled 11 per cent. The Kr 85 technique is simpler technically and requires less blood, instrumentation, and calculation than the standard dye techniques.
Modulation of Renal Cortical Blood Flow During Static Exercise in Humans
Authors: Holly R. Middlekauff, Egbert U. Nitzsche, Alison H. Nguyen, Carl K. Hoh, G. Gary Gibbs
Journal: Circulation Research (1997)

During static exercise, several reflex systems that increase sympathetic nerve activity, heart rate, arterial pressure, and cardiac output are activated. At rest, the renal circulation receives the most blood flow per tissue weight of any organ in the body. However, the renal circulatory response to static exercise has not been studied in humans because of technical limitations in methods for measuring rapid changes in renal blood flow. The aim of this study was to determine the renal blood flow response to static exercise in healthy humans and, specifically, to clarify the reflex mechanisms underlying this response. Renal cortical blood flow was measured using dynamic positron emission tomography and the blood flow agent oxygen-15 water. Graded handgrip exercise, posthandgrip circulatory arrest, and administration of intra-arterial adenosine were performed to clarify the mechanisms controlling renal blood flow during static exercise. The major new findings in this study are that in healthy humans (1) renal cortical blood flow decreases (basal versus handgrip, 4.4±0.1 versus 3.5±0.1 mL·min −1 ·g −1 ; P =.008) and renal cortical vascular resistance increases (basal versus handgrip, 17±1 versus 26±2 U; P =.01) in response to static handgrip exercise; (2) central command and/or the mechanoreflex contributes importantly to the early decrease in renal blood flow (basal versus handgrip, 4.2±0.2 versus 3.5±0.3 mL·min −1 ·g −1 ; P =.04) and to the increase in renal cortical vascular resistance (basal versus handgrip, 20±1 versus 25±2 U; P =.04); (3) the muscle metaboreflex contributes to further decreases in renal blood flow (basal versus posthandgrip circulatory arrest, 4.3±0.1 versus 3.5±0.2 mL·min −1 ·g −1 ; P =.002) and increases in renal cortical vascular resistance (basal versus handgrip, 18±1 versus 25±3 U; P =.002); and (4) exogenous adenosine activates the muscle metaboreflex producing reflex renal vasoconstriction and decreased renal blood flow, which may implicate endogenous adenosine generated during ischemic exercise as a potential activator of the muscle metaboreflex during ischemic handgrip exercise.
Studies in vivo of the ileocaeco-colic sphincter in the cat and dog
Authors: R. J. Jarrett, J. C. Gazet
Journal: Gut (1966)

EDITORIAL SYNOPSiS A study of the response of the ileocaeco-colic sphincter2 of the cat and dog to sympathomimetic and parasympathomimetic drugs and to stimulation of the autonomic nerves is reported.The response to drugs in vivo is identical with that previously noted in vitro, namely, contraction of the sphincter by adrenaline, noradrenaline, and acetylcholine, and relaxation by isoprenaline.Stimulation of the sympathetic nerves consistently resulted in contraction of the sphincter, but stimulation of the parasympathetic nerves (vagus) sometimes resulted in contraction and at other times relaxation of the sphincter.In view of the presence of P receptors in the sphincter, which, when stimulated cause relaxation of the muscle, it is suggested that the vagus contains adre- nergic nerves which supply these receptors.
Repolarization alternans: implications for the mechanism and prevention of sudden cardiac death
Authors: Mariah L Walker, David S Rosenbaum
Journal: Cardiovascular Research (2003)

For nearly 100 years, beat to beat alternation of T wave amplitude, termed T wave alternans (TWA), has been closely linked to electrical instability in the heart. TWA is now established among the strongest markers of susceptibility to sudden cardiac death. Since computer technology allows for detection of very subtle yet clinically significant TWA during standard exercise testing, TWA has been used increasingly as a noninvasive clinical tool for identifying and treating patients at risk for sudden cardiac death. The observation of TWA hastening ventricular tachyarrhythmias in an extraordinary variety of clinical and experimental conditions suggest potential universality of TWA in the pathophysiological mechanism of sudden death. High resolution optical mapping studies have shown that TWA arises from alternans of repolarization at the level of the ventricular myocyte. Cellular alternans is likely due to the actions of one or more ionic currents and is closely related to, if not directly dependent on, the kinetics of intracellular calcium cycling. Impairment in calcium cycling at the cellular and sub-cellular levels has been implicated in the mechanism of cellulcar alternans. Importantly, spatially discordant alternans between cells is most likely a consequence of heterogeneities of electrophysiological properties between cells which span the ventricular wall, serving to amplify spatial heterogeneities of repolarization, and forming a substrate for reentrant excitation. Through this mechanism, TWA is linked directly and mechanistically to the pathogenesis of arrhythmias. Although available data would suggest that TWA is certainly closely related to a mechanism of arrhythmogenesis, and is a strong marker of clinical risk, the precise sequence of events which triggers sudden cardiac death, and the potential role of TWA in this process remains elusive.
Two-dimensional contrast echocardiography. I. In vitro development and quantitative analysis of echo contrast agents
Authors: Steven B. Feinstein, Folkert J. Ten Cate, Werner Zwehl, Kenneth Ong, Gerald Maurer, Chuwa Tei, Pravin M. Shah, Samuel Meerbaum, Eliot Corday
Journal: Journal of the American College of Cardiology (1984)
TWO CASES OF TRAUMATIC ANEURYSM OF THE COMMON CAROTID
Authors: R. Jamison
Journal: BMJ (1919)

CAROTID. DxICA BnU; 489 able to apply their nowledge not merely to the improving of old methods of treatment, -but also to the devising of new methods to meet the new oonditions they had to deal with and the new environment in which they found themselves.
1981: A milestone for heart-lung transplants
Authors: Phil Gunby
Journal: JAMA (1981)

Four human heart-lung transplants have been performed this year at Stanford University Medical Center, Palo Alto, Calif—one more than in all the previous history of this procedure. Three of the four patients are still alive.  The other three such operations were carried out in the late 1960s and early 1970s (although development of the surgical techniques and early animal studies associated with heart-lung transplants date back to the 1940s and 1950s) and did not enjoy the same success. The first recipient apparently was a 2 1/2-month-old girl who was admitted to Texas Children's Hospital, Houston, with an atrioventricular canal defect and pulmonary hypertension. Because the infant's condition was considered to be nearly terminal, on Sept 15, 1968, Denton A. Cooley, MD, and colleagues transplanted into the infant the heart and lungs of a day-old anencephalic infant who was being maintained on a ventilator. The recipient infant died from pulmonary insufficiency
Prediction of chemical absorption into and through the skin from cosmetic and dermatological formulations
Authors: S. Grégoire, C. Ribaud, F. Benech, J.R. Meunier, A. Garrigues-Mazert, R.H. Guy
Journal: British Journal of Dermatology (2008)

To date, risk assessment following topical exposure to cosmetic/dermatological formulations cannot be precisely evaluated.To provide a tool for optimization of active permeation into/through skin and for risk assessment.A predictive model was developed for estimating the cumulative mass of a chemical absorbed into and across the skin from a cosmetic/dermatological formulation. Account was taken of (i) the ionization state of the chemical, to correct the skin/vehicle partition coefficient; and (ii) the nature of the cosmetic/dermatological formulation. Three specific assumptions were made: firstly, steady-state transport across the skin was achieved despite application of a finite dose of chemical; secondly, vehicle effects were small relative to the precision of the prediction; and, thirdly, each formulation could be treated as an oil-in-water emulsion, in which only that fraction of the chemical in the aqueous phase was available to partition into the stratum corneum. A database of 101 ex vivo human skin experiments involving 36 chemicals was analysed.For 91% of the data, the difference between predicted and experimental values was less than a factor 5; when the aforementioned corrections were not used, on the other hand, only 26% of the data was well predicted. The model was successfully applied to predict skin absorption of two compounds not included in the database, for which in vitro percutaneous penetration from cosmetic vehicles have been measured.A model has been developed to predict the mass of a chemical absorbed into and through the skin from a cosmetic or dermatological formulation.
Expression and role of FLT3 in regulation of the earliest stage of normal granulocyte-monocyte progenitor development
Authors: Charlotta Böiers, Natalija Buza-Vidas, Christina T. Jensen, Cornelis J. H. Pronk, Shabnam Kharazi, Lilian Wittmann, Ewa Sitnicka, Anne Hultquist, Sten Eirik W. Jacobsen
Journal: Blood (2010)
Early Morphine Administration to Expedite Gallbladder Visualization During Cholescintigraphy for Acute Cholecystitis
Authors: Dwight M. Achong, Luis E. Tenorio
Journal: Clinical Nuclear Medicine (2003)

A 58-year-old woman underwent emergent hepatobiliary imaging for evaluation of possible acute calculous cholecystitis. Intravenous morphine was administered 10 minutes after small bowel activity was first seen. The gallbladder visualized promptly after morphine administration, effectively excluding cystic duct obstruction and acute cholecystitis. The entire imaging procedure was completed and a final diagnosis made within 30 minutes.
A purchaser experience of managing new expensive drugs: interferon beta
Authors: E Rous, A Coppel, J Haworth, S Noyce
Journal: BMJ (1996)

Interferon beta is a new and expensive drug for treating multiple sclerosis. One published trial has shown that it reduces the exacerbation rate in patients who have relapsing-remitting disease without important disability. This paper describes the development of a strategy for purchasing the drug in one region of England before its licensing. Purchasers felt unable to decline funding for this marginally effective drug and thereby undertake explicit rationing. To ensure prescribing was within the guidelines, a vast communication network had to be sustained with managers, general practitioners, neurologists, the Multiple Sclerosis Society, and professional advisers in all the purchasing authorities. The workload involved was considerable. The dilemma of rationing in a public service with a high political profile is demonstrated.
An Address on SOME ALARMING SEIZURES
Authors: J. A. Ryle
Journal: BMJ (1934)

In the course of medical practice we are confronted from time to time by peculiar  seizures  or  nerve storms, which lack conformity with the more familiar descriptions. Some of these seizures cause great alarm to their victims, in that they seem to threaten paralysis, speechlessness, unconsciousness, or even death itself, or because they occasion profound states of instability and prostration. The appearance and sufferings of the patients during these attacks may further alarm relatives or onlookers, and even the medical man, unless he be familiar with the true nature of the  seizures  or fully alive to the history of the case, may be taken unawares, and feel so dubious about their purport and outcome as to be unable to give a reassuring prognosis. And yet the seizures which I have in mind are all consistent with long life and with good health at other times. Those with the more local effects may simulate or suggest organic disease of the brain ; those causing serious instability may also be wrongly attributed to cerebral vascular disease or cerebral tumour ; those which cause
Canonical and noncanonical Hedgehog pathway in the pathogenesis of multiple myeloma
Authors: Simona Blotta, Jana Jakubikova, Teresa Calimeri, Aldo M. Roccaro, Nicola Amodio, Abdel Kareem Azab, Umberto Foresta, Constantine S. Mitsiades, Marco Rossi, Katia Todoerti, Stefano Molica, Fortunato Morabito, Antonino Neri, Piersandro Tagliaferri, Pierfrancesco Tassone, Kenneth C. Anderson, Nikhil C. Munshi
Journal: Blood (2012)
Experience with Portacaval Shunt for Portal Hypertension
Authors: George E. Wantz, Mary Ann Payne
Journal: New England Journal of Medicine (1961)

SINCE the beginning of our experience with the surgical treatment of portal hypertension, we have believed that the operation of choice is portacaval shunt and that splenorenal shunts, because they are small and so frequently inadequate, should be restricted to patients with portal veins unsuitable for anastomosis to the inferior vena cava.§ There is abundant evidence that such a procedure is followed by the disappearance of esophagogastric varices and therefore the elimination of the hazards of massive varical hemorrhage. Although this is a laudable surgical achievement, critical analysis suggests that the problem of portal hypertension is not as simple as . . .
Effect of Protein Ingestion on the Glucose and Insulin Response to a Standardized Oral Glucose Load
Authors: Frank Q Nuttall, Arshag D Mooradian, Mary C Gannon, Charles Billington, Phillip Krezowski
Journal: Diabetes Care (1984)

Type II diabetic subjects were given 50 g protein, 50 g glucose, or 50 g glucose with 50 g protein as a single meal in random sequence. The plasma glucose and insulin response was determined over the subsequent 5 h. The plasma glucose area above the baseline following a glucose meal was reduced 34% when protein was given with the glucose. When protein was given alone, the glucose concentration remained stable for 2 h and then declined. The insulin area following glucose was only modestly greater than with a protein meal (97 +/- 35, 83 +/- 19 microU X h/ml, respectively). When glucose was given with protein, the mean insulin area was considerably greater than when glucose or protein was given alone (247 +/- 33 microU X h/ml). When various amounts of protein were given with 50 g glucose, the insulin area response was essentially first order. Subsequently, subjects were given 50 g glucose or 50 g glucose with 50 g protein as two meals 4 h apart in random sequence. The insulin areas were not significantly different for each meal but were higher when protein + glucose was given. After the second glucose meal the plasma glucose area was 33% less than after the first meal. Following the second glucose + protein meal the plasma glucose area was markedly reduced, being only 7% as large as after the first meal. These data indicate that protein given with glucose will increase insulin secretion and reduce the plasma glucose rise in at least some type II diabetic persons.
Aspirin for the Primary Prevention of Myocardial Infarction
Authors: Arnold S. Relman
Journal: New England Journal of Medicine (1988)

Under the somewhat ill-defined rubric "Special Report," we publish in this week's issue a preliminary report from the Physicians' Health Study, a double-blinded, controlled trial of aspirin in the prevention of cardiovascular disease and of beta carotene in the prevention of cancer.1 After more than 59,000 volunteers were screened, 22,000 male U.S. physicians 40 to 84 years of age were entered in the trial and randomly assigned to receive one of four treatments: (1) buffered aspirin (325 mg) and beta carotene (50 mg), (2) buffered aspirin and beta carotene placebo, (3) aspirin placebo and beta carotene, and (4) aspirin placebo . . .