tbuckley/cabot-search huggingface dataset:
Endogenous generation of reactive oxidants and electrophiles and their reactions with DNA and protein
Authors: Lawrence J. Marnett, James N. Riggins, James D. West
Journal: Journal of Clinical Investigation (2003)

A constellation of reactive intermediates -electrophiles and free radicals -capable of damaging cellular constituents is generated during normal physiological or pathophysiological processes.The consequences of this damage include enhanced mutation rates, altered cell signaling, and events summarized in other articles in this Perspective series.In many cases, the initially generated reactive intermediates convert cellular constituents into second-generation reactive intermediates capable of inducing further damage.Cells have adapted to the existence of reactive intermediates by the evolution of defense mechanisms that either scavenge these intermediates or repair the damage they cause.High levels of damage can lead to cell death through apoptosis or necrosis.This article provides an overview of DNA and protein damage by endogenous electrophiles and oxidants and an introduction to the consequences of this damage.
Another way to tame the monster
Authors: Peter R Mansfield
Journal: BMJ (2006)

EDITOR—The Angell-Spence-Godlee proposal to ban pharmaceutical manufacturers from researching their products has considerable merit.1 However, Healthy Skepticism advocates a more comprehensive alternative that will also reduce the harm currently caused by misleading promotion, biased industry funding of education, and high drug prices. Our alternative is also more politically achievable because implementation can be government revenue neutral while securing long term competitive return on investment for the …
Forearm injury in a 5 year old boy
Authors: R. Coomber, G. Cuffolo, Y. Kalairajah, S. Burtt, R. Bhumbra
Journal: BMJ (2013)

A 5 year old right hand dominant boy was brought to the emergency department by his mother because of a painful and deformed left forearm. After slipping in the snow he had landed on his outstretched left hand. He had no relevant medical history. On examination, he was stable and the deformed arm was an isolated injury. There were no symptoms of neurovascular compromise and no evidence of skin compromise or breach.

Plain radiographs were obtained (fig 1⇓).



Fig 1 Anterioposterior (top) and lateral (bottom) radiographs of the forearm and elbow 





### 1 What abnormality do the radiographs show?

#### Short answer

The radiographs show a minimally displaced proximal third ulna diaphyseal fracture and a radial head dislocation. The eponymous term for this injury is a Monteggia fracture of the forearm.

#### Long answer

The Monteggia fracture was first described by Monteggia in 1814.1 The radial head can be dislocated anteriorly, laterally, or posteriorly, and these injuries can be found in both adults and children. The Bado classification is used to describe the radiographic appearance of a Monteggia fracture (fig 2⇓).



Fig 2 Bado classification of Monteggia fractures



These injuries are often missed because they are rare, accounting for less than 5% of all forearm fractures. They …
Comment on Monnier et al. Magnitude of the Dawn Phenomenon and Its Impact on the Overall Glucose Exposure in Type 2 Diabetes: Is This of Concern? Diabetes Care 2013;36:4057–4062
Authors: Richard D. Carr, Charles M. Alexander
Journal: Diabetes Care (2014)

The recent publication by Monnier et al. (1) on the magnitude of the dawn phenomenon in patients with type 2 diabetes highlights the need to effectively treat early morning hyperglycemia. However, we wish to comment on the authors’ classification system for oral antihyperglycemic agents. The authors categorized dipeptidyl peptidase-4 (DPP-4) inhibitors, along with sulfonylureas and glinides, as insulin secretagogues and metformin and thiazolidinediones as insulin sensitizers. While others have also used this approach, we feel that this classification may be misleading as it does not fully reflect the mechanism of action of incretin agents, including GLP-1 receptor agonists and DPP-4 inhibitors, and may erroneously lead …
Isometric contractions studied in the isovolumically beating dog heart
Authors: K PETTERSSON, A J DRAKE-HOLLAND, M I M NOBLE
Journal: Cardiovascular Research (1985)

Journal Article Isometric contractions studied in the isovolumically beating dog heart Get access K PETTERSSON, K PETTERSSON Search for other works by this author on: Oxford Academic PubMed Google Scholar A J DRAKE-HOLLAND, A J DRAKE-HOLLAND ††Department of Medicine 1 St George's Hospital Medical School, London SW17 ORE; Search for other works by this author on: Oxford Academic PubMed Google Scholar M I M NOBLE M I M NOBLE ‡‡King Edward VII Hospital, Midhurst West Sussex GU29 0BL Search for other works by this author on: Oxford Academic PubMed Google Scholar Cardiovascular Research, Volume 19, Issue 9, September 1985, Page 521, https://doi.org/10.1093/cvr/19.9.521 Published: 01 September 1985
Soluble E-selectin and eosinophil cationic protein are distinct serum markers that differentially represent clinical features of atopic dermatitis
Authors: None FURUE, None KOGA, None YAMASHITA
Journal: British Journal of Dermatology (1999)

The serum levels of eosinophil cationic protein (ECP), soluble E‐selectin (sE‐selectin), soluble CD14 (sCD14) and interleukin (IL)‐4 are known to be elevated in patients with atopic dermatitis (AD). However, little is known of the mutual relationship between these factors. To elucidate the clinical and mutual relevance of these markers, we examined the serum levels of ECP, sE‐selectin, sCD14 and IL‐4 as compared with eruption scores, itch scores, total IgE and numbers of peripheral eosinophils in patients with AD (n = 43), non‐atopic eczema (n = 24) and urticaria (n = 13) and in normal individuals (n = 45). In 27 patients with AD the levels of these markers were compared before and after treatment. Levels of ECP were elevated only in the patients with AD, whereas the sE‐selectin levels were higher not only in AD but also in non‐atopic eczema in a severity‐dependent manner. The levels of both markers significantly diminished after treatment. Significant correlations existed between ECP levels and numbers of eosinophils, sE‐selectin levels and itch scores, and sE‐selectin levels and IgE levels. No significant changes were observed in the sCD14 and IL‐4 levels. Taken together, sE‐selectin and ECP are good but distinct serum markers that reflect different clinical features of AD.
ABC of 1 to 7. Poisoning.
Authors: H B Valman
Journal: BMJ (1982)

Accidental swallowing of drugs and household fluids is common among children, especially between the ages of 2 and 3 years.Most of them take Identification Guide trivial amounts of drugs, but every child must be assessed carefully to H K L ensure that effective treatment is given when a potentially fatal dose has been swallowed.A health visitor's report on the family may be helpful as ) \)P ) the event may indicate a chaotic household or a non-accidental injury.50B0 587 270Child-resistant containers have reduced the incidence of poisoning by tablets.(¢>(fl (The name of the drug may be on the bottle, or the tablets may be identifiable from charts.The prescriber, hospital pharmacist, or the 276 277 278pharmacist who dispensed the tablets may be able to help.The time the 6 i drug was taken should be written in the clinical notes and whether any symptoms such as vomiting have occurred.The maximum amount of drug 5 287 288 that could have been taken should be estimated.The original number of ~: tablets in the bottle may be known.Usually the dispensing pharmacist knows the original number of tablets dispensed.Initially, maintaining adequate ventilation and circulation is more important than making an exact diagnosis.The level of consciousness is the most important single sign.The frequency and depth of the respiratory movements are noted.Slow shallow movements suggest impending respiratory arrest and the need for assisted ventilation.A low blood pressure indicates that cardiac arrest is imminent.Particles of tablets may be present in the mouth or vomit.The odour of paraffin (kerosene) may be present in the breath.Caustic or acid substances may cause burns on the lips and tongue and in the mouth.Deep sighing respiratory movements or a raised respiratory rate suggests salicylate poisoning, while tachycardia and dilated pupils are found in atropine poisoning.Opiates cause constriction of the pupils.
CHARACTERIZATION OF COMPOUND HETEROZYGOSITY FOR MUTATIONS R269W IN KCNH2 AND P1824A IN SCN5A ASSOCIATED WITH LONG QT SYNDROME AND SINUS NODE DYSFUNCTION
Authors: Kenshi Hayashi, Noboru Fujino, Katsuharu Uchiyama, Tetsuo Konno, Akihiko Hodatsu, Toyonobu Tsuda, Hidekazu Ino, Yasutaka Kurata, Haruhiro Higashida, Masakazu Yamagishi
Journal: Journal of the American College of Cardiology (2011)
Mutations in the PI3K/PTEN/TSC2 Pathway Contribute to Mammalian Target of Rapamycin Activity and Increased Translation under Hypoxic Conditions
Authors: Fiona Kaper, Nadja Dornhoefer, Amato J. Giaccia
Journal: Cancer Research (2006)

Abstract Decreased oxygen causes a rapid inhibition of mRNA translation. An important regulatory mechanism of translational repression under hypoxic conditions involves inhibition of the mammalian target of rapamycin (mTOR). mTOR is a target of the phosphatase and tensin homologue detected on chromosome 10 (PTEN)/phosphatidylinositol 3-kinase/AKT/TSC2 pathway, a pathway that is frequently mutated in human cancers. Although hypoxia has been shown to inhibit mTOR activity, we show here that the hypoxia-induced inhibition of mTOR activity is attenuated in cells lacking TSC2 or PTEN, resulting in a higher translation rate even under hypoxic conditions. Comparison of mTOR inhibition by hypoxia alone or in combination with rapamycin showed that prolonged exposure to hypoxia was required to fully inhibit mTOR activity even in wild-type cells. Increased mTOR activity and protein synthesis did not translate into enhanced cell proliferation rates. However, lack of TSC2 resulted in a survival advantage when cells were exposed to hypoxia. Protection against hypoxia-induced cell death due to TSC2 deficiency is rapamycin-resistant, suggesting that TSC2 affects an apoptotic pathway. Tumors derived from TSC2 wild-type cells exhibited a growth delay compared with TSC2-deficient tumors, indicating that enhanced mTOR activity is advantageous in the initial phase of tumor growth. Therefore, failure to inhibit mTOR under oxygen-limiting conditions can be affected by upstream activating mutations and increases the survival and growth of hypoxic tumor cells. (Cancer Res 2006; 66(3): 1561-9)
The Guinea Pig Syndrome: Improving Clinical Trial Participation among Thoracic Patients
Authors: Gwendolyn P. Quinn, Bethany A. Bell, Miriam Y. Bell, Vicki D. Caraway, Diane Conforte, Linda B. Graci, Valerie L. Powell-Stafford, Amber L. Sapp, Cynthia O. Shimizu, Elizabeth J. Vaughn, Charles Williams, Gerold Bepler
Journal: Journal of Thoracic Oncology (2007)
Crybabies—Coping With Colic: What to Do When Baby Won't Stop Crying
Authors: Leslie L. Barton
Journal: JAMA (1985)

Colic occurs in approximately 20% of all infants during their first few months of life. Because it is a problem, both frequent and disruptive, it is of importance to parents and child health care professionals. Yet, remarkably few well-controlled, carefully designed clinical and laboratory studies of colic have been performed. Dr Weissbluth has carried out such investigations and, in this small volume, succinctly presents the thesis that grew out of his work with parents and their colicky infants. The book contains 14 chapters. It begins with the definition of colic, prolonged "inconsolable crying" in an otherwise well infant. The author reviews old theories on causation and criticizes statements from well-known pediatric behavioral scientists. He discusses basic concepts of temperament and sleep. Dr Weissbluth then presents and expands his theory that colic may represent a sleep disorder. Practical approaches to alleviating the effects of colic on the infant and family and
Radiation Dose-Reduction Program for Cardiac Computed Tomography Angiography
Authors: Felipe S. Torres
Journal: JAMA (2009)

1. Li D, Yeung SC, Hassan MM, Konopleva M, Abbruzzese JL. Antidiabetic therapies affect risk of pancreatic cancer. Gastroenterology. 2009;137(2):482-488. 2. Bonovas S, Filioussi K, Sitaras NM. Statins are not associated with a reduced risk of pancreatic cancer at the population level, when taken at low doses for managing hypercholesterolemia: evidence from a meta-analysis of 12 studies. Am J Gastroenterol. 2008;103(10):2646-2651.
Changes in fatty-acid composition of body fat before and after birth in Tanzania: an international comparative study.
Authors: E R Boersma
Journal: BMJ (1979)

Changes in the fatty-acid composition of human adipose tissue before birth and during infancy and childhood were studied in Tanzania and compared with data for British and Dutch infants in relation to their diet. From the 32nd to the 37th week of gestation in Tanzania the proportion in the body fat of the unsaturated fatty acid linoleic acid tended to rise, suggesting an adequate supply of this essential fatty acid from the mother to the fetus. At term 2.5% of the total fatty acids of the body fat was linoleic acid, which corresponded with values in Dutch newborn infants but was significantly higher than those in British infants. During infancy in Tanzania the composition of the fat showed a dramatic increase in the proportions of the saturated fatty acids lauric acid and myristic acid, which did not occur in Dutch and British infants. The proportion of linoleic acid increased to 8%. These changes were a reflection of the fatty-acid composition of the fat in the human milk that the infants received. During weaning (1-2 years of age) the fatty-acid composition changed only slightly. The specific fatty-acid composition of the fat in Tanzanian breast milk may have a beneficial influence on the extent of intestinal absorption in the newborn child.
Cholesterol-Phospholipid Ratio in the Prediction of Coronary Heart Disease
Authors: H. Emerson Thomas, William B. Kannel, Thomas R. Dawber, Patricia M. McNamara
Journal: New England Journal of Medicine (1966)

THE role of lipids as predictors of coronary heart disease has become of considerable interest during the past two decades. Many individual lipids, such as the serum cholesterol, phospholipid and various beta-lipoprotein fractions, have been extensively evaluated as indicators of coronary heart disease. Attempts have also been made to combine certain of these lipid values in the hope of producing an index that would be a more sensitive predictor of the potential for developing coronary heart disease than the individual lipids. Included among these proposed lipid indexes are the ratio of cholesterol to phospholipid and that of the uric acid . . .
Initial North American experience with inoue balloon for percutaneous mitral valvuloplasty
Authors: J.M. Isner, K. Ramaswamy, Susan Kelly, A. Massumi, D. Holmes, J. Carroll, T. Feldman, R. Chisholm, P. Sundram, G. Dorros, S. Stertzer, W. O'Neil, K. Inoue
Journal: Journal of the American College of Cardiology (1990)
THE SURGERY OF COLITIS
Authors: F. C. Wallis
Journal: BMJ (1909)

THE SURGERY OF COLITIS.[JAN. 2, I909.of the ja+w, to an insignificant and bloodless operation, which can consequently be frequently performed without danger immediately after the neck operation.It enables the primary growth to be removed with greater precision.It does away with all necessity for preliminary laryngotomy or tracheotomy.It cuts off the blood supply to the tumour in the interval, if the operation has to be divided into two stages.It will possibly starve cancer cells which may be left behind after attempted extirpation of the disease.In my experience it is the key to the operation.The second principle is that a communication between ihe mouth and a large wound, in the neck should always be avoided whiere 1possible.Unless the disease be situated in the tonsil or its neighbourhood, and except the patient insist on a single operation, this can always be accomplished by dividing the operation into two stages in those cases in wlhich for the satisfactdry removal of the disease the lower jaw requires division.The neck, as before, is attacked first, and the lingual and facial arteries are tied.When, in a fortnight, the large wound in the neck is healed, the jaw is divided and the primary growth is excised, as before, bloodlessly.In conclusion, as regards final results, early diagnosis is the only hope.With this view, the therapeutic test of cancer, iodide of potassium, should be relegated to the limbo of dangerous playthings.Immediate microscopic examination of a piece of the growth should be the only test, and the tlherapeutic test should never be employed unless the microscopic report is doubtful.It should then be pushed rapidly, and its effects not watchied too long.
The Cancer Institute on the Griddle
Authors: Daniel S. Greenberg
Journal: New England Journal of Medicine (1978)

"I find it astonishing," said Senator George McGovern with uncharacteristic exasperation in his voice, "that even though the majority of cancers are preventable, the cancer research establishment doggedly continues to seek an elusive cancer 'cure.'"The setting for this loaded statement was a Senate hearing room, where last month the liberal South Dakota Democrat and an unlikely ally, Senator Robert Dole, a conservative Kansas Republican, inflicted a severe verbal beating on the National Institutes of Health and, in particular, the National Cancer Institute.McGovern, who chaired the Agriculture Committee's Subcommittee on Nutrition, has long been fascinated by what he sees . . .
Endonuclease Analysis of Viral DNA from Varicella and Subsequent Zoster Infections in the Same Patient
Authors: Stephen E. Straus, William Reinhold, Holly A. Smith, William T. Ruyechan, David K. Henderson, R. Michael Blaese, John Hay
Journal: New England Journal of Medicine (1984)

VARICELLA is a common exanthematous disease that affects most persons during childhood. Zoster is most prevalent in the elderly and is characterized by vesicular lesions similar to those of varicella but typically confined to a single cutaneous dermatome.1 A series of careful clinical and epidemiologic studies conducted over the past century have led to the recognition that varicella and zoster are closely related infections.2 3 4 Those observations and the determination that varicella and zoster viruses behave similarly on in vitro cultivation led Hope-Simpson to postulate that zoster represents a reactivated infection with varicella virus that has persisted in a latent form . . .
Extracellular matrix modulates sensitivity of hepatocytes to fibroblastoid dedifferentiation and transforming growth factor β-induced apoptosis
Authors: Patricio Godoy, Jan G. Hengstler, Iryna Ilkavets, Christoph Meyer, Anastasia Bachmann, Alexandra Müller, Gregor Tuschl, Stefan O. Mueller, Steven Dooley
Journal: Hepatology (2009)

Hepatocytes in culture are a valuable tool to investigate mechanisms involved in the response of the liver to cytokines. However, it is well established that hepatocytes cultured on monolayers of dried stiff collagen dedifferentiate, losing specialized liver functions. In this study, we show that hepatocyte dedifferentiation is a reversible consequence of a specific signaling network constellation triggered by the extracellular matrix. A dried stiff collagen activates focal adhesion kinase (FAK) via Src, leading to activation of the Akt and extracellular signal-regulated kinase (ERK) 1/2 pathways. Akt causes resistance to transforming growth factor beta (TGF-beta)-induced apoptosis by antagonizing p38, whereas ERK1/2 signaling opens the route to epithelial-mesenchymal transition (EMT). Apoptosis resistance is reversible by inhibiting Akt or Src, and EMT can be abrogated by blocking the ERK1/2 pathway. In contrast to stiff collagen, a softer collagen gel does not activate FAK, keeping the hepatocytes in a state where they remain sensitive to TGF-beta-induced apoptosis and do not undergo EMT. In this culture system, inhibition of p38 as well as overexpression of constitutively active Akt causes apoptosis resistance, whereas constitutively active Ras induces EMT. Finally, we show that matrix-induced EMT is reversible by replating cells from dried stiff to soft gel collagen. Our results demonstrate that hepatocyte dedifferentiation in vitro is an active process driven by FAK-mediated Akt and ERK1/2 signaling. This leads to similar functional and morphological alterations as observed for regenerating hepatocytes in vivo and is reversible when Akt and/or ERK1/2 signaling pathways are antagonized.Hepatocytes can exist in a differentiated and a dedifferentiated state that are reversible and can be switched by manipulating the responsible key factors of the signaling network.
Consultant is awarded 4.5m for race and sex discrimination
Authors: C. Dyer
Journal: BMJ (2011)

A consultant physician who was subjected to a concerted exercise to get rid of her by managers and senior clinicians at the NHS trust that employed her has been awarded a record compensation payout for discrimination of nearly £4.5m (€5.4m; $7m).

An employment tribunal awarded Eva Michalak, who qualified in Poland, the record sum for sex and race discrimination that wrecked her career and left her with enduring psychiatric injuries and unable to work again.

The award follows findings by the Leeds Employment Tribunal last year that Mid-Yorkshire Hospitals NHS Trust and three named employees of the trust were guilty of sex and race discrimination for their parts in her suspension and dismissal on the basis of complaints that were later shown to be without justification.

Dr Michalak, now 53, started work at the end …
Medical Therapy Alone Produces Regression of Combined Aortic and Mitral Valve Involvement in Hypereosinophilic Syndrome
Authors: Tetsushi Yamamoto, Tetsuari Onishi, Akihiro Kaneko, Kensuke Matsumoto, Nobuhide Hayashi, Shohiro Kinoshita, Seiji Kawano, Hiroya Kawai, Ken-ichi Hirata, Shunichi Kumagai
Journal: Circulation (2010)
Is the evidence for hyperbolic discounting in humans just an experimental artefact?
Authors: Glenn W. Harrison, Morten Igel Lau
Journal: Behavioral and Brain Sciences (2005)

We question the behavioral premise underlying Ainslie's claims about hyperbolic discounting theory. The alleged evidence for humans can be easily explained as an artefact of experimental procedures that do not control for the credibility of payment over different time horizons. In appropriately controlled and financially motivated settings, human behavior is consistent with conventional exponential preferences.
Current approaches to the treatment of metastatic brain tumours
Authors: Taofeek K. Owonikoko, Jack Arbiser, Amelia Zelnak, Hui-Kuo G. Shu, Hyunsuk Shim, Adam M. Robin, Steven N. Kalkanis, Timothy G. Whitsett, Bodour Salhia, Nhan L. Tran, Timothy Ryken, Michael K. Moore, Kathleen M. Egan, Jeffrey J. Olson
Journal: Nature Reviews Clinical Oncology (2014)