tbuckley/cabot-search huggingface dataset:
Abstract 4043: Loss of imprinting of KCNK9 in breast cancer
Authors: David A. Skaar, Victoria L. Seewaldt, Michael N. Gould, Randy L. Jirtle
Journal: Cancer Research (2012)

Abstract KCNK9 (TASK-3) encodes a two-pore potassium channel that functions in tumor growth and survival. The potassium channel function is necessary for tumor proliferation and survival, by enhancing resistance to hypoxia and apoptosis. KCNK9 overexpression is observed in melanoma, colorectal cancer, and breast and brain tumors, but with no associated mutations found. Rather, the overexpression is often the apparent result of gene amplification of KCNK9, but any other mechanism that increases expression would presumably have a similar effect on tumorigenesis. This importance of gene dosage and expression levels is particularly relevant, as KCNK9 has been demonstrated to be a maternally expressed imprinted gene, which, in effect, reduces copy number. Monoallelic expression of KCNK9 was originally found in brain tissue, but our work has found that it is also imprinted in breast tissue. Thus, we hypothesized that loss of imprint control would be similar to a gene duplication, increasing the effective copy number, and therefore KCNK9 gene expression. To study the regulation of KCNK9 imprinting in tumors, we have screened for differentially methylated regions that may function as imprint control regions (ICRs), and examined the expression status of KCNK9 in breast tumor samples relative to the methylation state of the putative ICRs. Approximately 40-50% of breast tumor samples analyzed show loss of imprinting, seen as expression of both alleles of an exonic polymorphism. Additionally, loss of methylation at a putative ICR upstream of the transcription start site is observed in combination with loss of imprint regulation. This correlated loss of methylation and imprint control is seen most commonly in tumors of the “triple negative” subtype - tumors negative for expression of estrogen receptor, progesterone receptor, and HER2/neu. These novel findings regarding KCNK9 imprint regulation and its disruption in a subset of tumors may lead to new approaches in diagnosis and targeted therapy of breast cancer. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 4043. doi:1538-7445.AM2012-4043
Administration of Troglitazone, but Not Pioglitazone, Reduces Insulin Resistance Caused by Short-Term Dexamethasone (DXM) Treatment by Accelerating the Metabolism of DXM
Authors: Hiroshi Morita, Yutaka Oki, Takeshi Ito, Hiroko Ohishi, Sadako Suzuki, Hirotoshi Nakamura
Journal: Diabetes Care (2001)

Thiazolidine derivatives are newly developed insulin sensitizer agents that act to lower plasma glucose and reduce hyperinsulinemia (1), and they are being used to treat patients with type 2 diabetes accompanying insulin resistance. However, the precise molecular mechanism by which thiazolidines counteract general insulin resistance has yet to be clarified. Glucocorticoid induces gluconeogenesis and insulin resistance, resulting in the development of diabetes (2), but the precise molecular mechanisms remain to be elucidated. Recent studies showed that troglitazone, which was the first clinically applied drug of thiazolidine derivatives, improved dexamethasone (DXM)-induced insulin resistance in rats in a glucose clamp study (3) and that it had a good effect on patients with glucocorticoid-induced diabetes (4). In the present study, we examined the effects of troglitazone and pioglitazone, another insulin sensitizer, on insulin resistance induced by short-term DXM treatment, and compared their effects with those of metformin. Furthermore, troglitazone has been reported to reduce the plasma concentration of the oral contraceptives ethinylestradiol and norethindrone, which are metabolized by the liver enzyme CYP3A4 (5). Troglitazone is also believed to be an inducer of CYP3A4 like rifampicin and phenytoin, and it has been speculated that troglitazone may reduce the effects of glucocorticoid, which is metabolized by CYP3A4, by enhancing the activity of CYP3A4. In this study, we investigated the effects of troglitazone and pioglitazone on …
Open letter from a carer
Authors: A. M. Jayes
Journal: BMJ (1996)

Thank you for giving me the opportunity to comment on your draft proposals for continuing care health provision. On behalf of carers I am concerned that the eligibility criteria for palliative care have not yet been finalised. And the word “dying” is ominously present.

Carers seem to get only a politically correct mention in your document. Carers are the people who are trying long term, usually alone, to darn torn lives into something bearable—at the blunt end of chronic illness or disability. And it is a blunt situation. After all, no one talks of carers for people with disabilities or illnesses from which they are likely to recover. Carers are people who are dealing with the obverse, mucky, side of the embroidery of life's rich pattern.

Can you imagine how lonely this is? Nurses in hospitals, or even residential homes, have regular support when they are on duty, which is not for the bulk of their waking hours. …
Interleukin-10 Expression in Macrophages during Phagocytosis of Apoptotic Cells Is Mediated by Homeodomain Proteins Pbx1 and Prep-1
Authors: Elaine Y. Chung, Jianguo Liu, Yoichiro Homma, Yunhua Zhang, Andrea Brendolan, Matilde Saggese, Jihong Han, Roy Silverstein, Licia Selleri, Xiaojing Ma
Journal: Immunity (2007)
ATPase activity of the cross-linked complex between cardiac myosin subfragment 1 and actin in several models of chronic overloading. A new approach to the biochemistry of contractility.
Authors: B Lauer, N Van Thiem, B Swynghedauw
Journal: Circulation Research (1989)

Myosin ATPase activity is usually considered to reflect the contractile capacity of a given muscle since it correlates with the maximum initial speed of shortening of the unloaded muscle (Vmax). There are several exceptions to this scheme, and it was the goal of this study to determine if the Mg2+-ATPase activity of the covalently bound actomyosin S1 is a more physiological index of contractility. On polyacrylamide gels, the complex obtained after condensation of fast skeletal myosin S1 to skeletal actin is identical to that obtained with myosin S1 from the ventricles of different species, including rat, guinea pig, and human, cross-linked to cardiac or skeletal actin. In every condition, the ATPase activity of the complex is 700-fold higher than that of myosin S1. It correlates linearly with the Vmax both in phylogeny and in conditions in which an isomyosin shift has been reported, such as hypothyroidism and chronic cardiac overload. Such a relation indicates that, in species that already have a low Vmax, a small change in myosin ATPase may induce dramatic consequences in the shortening velocity. Cardiac hypertrophy in humans, where the drop in Vmax is not associated with a myosin change, does not fit into this scheme. The enzymatic activity of the complex is also unmodified in this condition, which shows that, in humans, the myosin ATPase is not a determinant of Vmax and suggests that other mechanisms may be involved. Measurement of this type of ATPase activity provides a new tool to explore contractility biochemically, which is more reproducible and, from a technical point of view, easier to perform than a kinetic assay. It also correlates better with mechanical data obtained with skinned fibers than with those measured on fresh papillary muscles.
The New Global Threat: Severe Acute Respiratory Syndrome and its Impacts
Authors: Richard Kirk
Journal: BMJ (2004)

This collection of essays by public health doctors, academics, and clinicians attempts to record the cultural and political substrate necessary for SARS (severe acute respiratory syndrome) to cross species and continents. It documents the public health challenges in containing the disease and identifying its cause, and additionally reflects upon the social and economic impact.

It is now thought that SARS is a zoonosis that originated in the …
Interview with National Health Information Technology Coordinator David Brailer, MD, PhD
Authors: Anne Harding
Journal: BMJ (2004)

Before becoming the United States' first information technology czar on May 6, Dr David J Brailer was senior fellow at the Health Technology Center in San Francisco, and spent 10 years as CEO and chairman of CareScience, Inc. He received his medical degree from the University of Pennsylvania and a doctorate in economics from the Wharton School. This July, Dr Brailer released a strategic plan with four major goals for his office: placing electronic health records in physicians' hands, developing a national interconnectivity network, boosting consumer access to personal health information, and improving surveillance and monitoring related to population health improvement. This month, BMJ spoke to Dr Brailer about the state of health information technology in this country and the future.

We're now identifying the key priorities that are the precursors to many of the other steps, and… setting up a variety of federal teams and even private sector initiatives to move forward key elements of the plan. There's a health care technology leadership panel of Fortune 50 manufacturing, transportation, and financial services CEOs coming together to make commentary on the macroeconomic conditions with health information technology adoption. There is an internal budget process that's being worked through to determine whether or not a proposal will be made to Congress for investment in this area. There are …
Neurological complications associated with parenteral treatment: central pontine myelinolysis and Wernicke's encephalopathy.
Authors: P D Thompson, R F Gledhill, N P Quinn, M N Rossor, P Stanley, E N Coomes
Journal: BMJ (1986)

Infusion of intravenous fluids is part of the routine management of patients presenting with severe metabolic and electrolyte derange- ments.Usually such treatment is free ofneurological complications, but under certain circumstances these patients may develop two potentially serious disorders-namely, central pontine myelinolysis and Wernicke's encephalopathy.'Our recent experience of three such patients, two of whom had both central pontine myelinolysis and Wernicke's encephalopathy while the third had central pontine myelinolysis alone, suggests that these conditions may be more common than is generally thought.We report on these patients to highlight the circumstances in which these two complications arose as both may be prevented by timely intervention. Case Reports CASE 1An 18 year old woman presented with lethargy in the 20th week of her second pregnancy.She had vomited at least 10 times daily throughout gestation and had lost 1-3 kg in weight.She was able to walk into the emergency room, and on examination had no abnormal neurological signs but was pale and dehydrated.The plasma sodium concentration was 126 mmol(mEq)/l, plasma potassium 2 3 mmol(mEq)/l, and blood urea 86 5 mmol/l (519 mg/100 ml).During the first two hospital days she received 16 litres of intravenous fluid, comprising 10 litres of physiological saline (154 mmol sodium/l) and 6 litres of 5% dextrose.She was also given transfusions of four units of packed red blood cells.After these measures the plasma sodium concentration was 145 mmol/l, potassium 4 mmol/l, and blood urea 14-7 mmol/l (88 mg/100 ml).On the fourth hospital day she did not speak or respond to verbal commands, and the next day she was irritable and confused.Bilateral abducens palsies, horizontal nystagmus, and bilateral weakness of the lower face were present.The corneal reflexes were normal.She moved all limbs spontaneously, but the left plantar response was extensor.Parenteral thiamine (250 mg) was administered, and the next day the abnormal ocular movements were less pronounced.Over the next two weeks her mental state improved but neurological examinations showed the evolution of a spastic quadriparesis.By the 17th hospital day she was alert and it became apparent that she had severe spastic dysarthria and intact sensation.Thereafter her neurological deficits rapidly improved, and eight weeks after admission she
Intraventricular Cardiac Massage
Authors: Jack L. Ratliff
Journal: JAMA (1971)

<h3>To the Editor.—</h3> Several methods have been investigated for assisting the failing heart. Clauss et al have studied external counter pulsation techniques. Brown et al and Schilt and others have worked with intraaortic balloon pumping to augment cardiac output. Dennis et al, among others, have worked with the body squeezer or external counter pulsation technique in an attempt to augment cardiac output and relieve the work load of the heart. Venoarterial perfusion with membrane gas exchange has received considerable attention recently. None of the above methods has earned wide application because of their various disadvantages. We have been evaluating right ventricular balloons. When inflated they evacuate blood from the right side of the heart, displace the interventricular septum to the left, and therefore evacuate blood from the left side of the heart. In both the fibrillating animal and the fibrillating heart-lung preparation this method of cardiac assistance has produced significant
Repetita iuvant – INTACC (Intergruppo Italiano Terapia Adiuvante Carcinoma del Colon)
Authors: F. Di Costanzo, S. Gasperoni, A. Falcone, L. Dogliotti, L. Frassinetti, P. Bruzzi, R. Rosso
Journal: Annals of Oncology (2001)
A Diabetic Subject With MELAS and Antiphospholipid Syndrome
Authors: Hung-Yuan Li, Wei-Shiung Yang, Tong-Yuan Tai, Lee-Ming Chuang
Journal: Diabetes Care (2003)

Mitochondrial encephalopathy, lactic acidosis, and stroke-like episodes (MELAS) syndrome has been reported to coexist with autoimmune type 1 diabetes (1) and Graves’ disease (2). We described, for the first time, a diabetic patient with MELAS syndrome, autoimmune hemolytic anemia, and antiphospholipid syndrome.

During routine health examination, a 38-year-old man was diagnosed with diabetes. There was no family history of diabetes. On 22 January 2001, he was admitted due to right hemiparesis, slurred speech, and headache. Magnetic resonance imaging of the brain revealed increased signal intensity on diffusion scan with decreased apparent …
Blood Transfusion for Gastrointestinal Bleeding
Authors: Loren Laine
Journal: New England Journal of Medicine (2013)

Gastrointestinal bleeding accounts for more than 450,000 hospitalizations annually in the United States1 and is a frequent indication for red-cell transfusion. Blood transfusions are given to 43% of patients hospitalized with upper gastrointestinal bleeding in the United Kingdom2 and to 21% of patients hospitalized with lower gastrointestinal bleeding in the United States.3 Transfusion practices for patients with gastrointestinal bleeding have fluctuated over the past 100 years. Avoidance of transfusions early in the 20th century, owing to concern that increased blood pressure would induce rebleeding, gave way to more liberal use of transfusions,4 and a hemoglobin threshold for transfusion of 10 . . .
WITHDRAWN: Genetic Effect Of Single-Nucleotide Polymorphisms In The PPARGC1B Gene On Airway Hyperreactivity In Asthmatic Patients
Authors: Jong-Sook Park, Myung-Sin Kim, Sung-Woo Park, An-Soo Jang, Choon-Sik Park
Journal: Journal of Allergy and Clinical Immunology (2014)
Effectiveness of Acupuncture
Authors: George Mendelson
Journal: JAMA (1981)

<h3>To the Editor.—</h3> In his comment about acupuncture treatment for pain relief, George A. Ulett, MD (1981; 245:768), fails to mention controlled studies of acupuncture that have shown that acupuncture is no more effective than placebo in the relief of chronic pain (1975;232:1133).<sup>1,2</sup> Although scientific explanations of the mechanism of acupuncture analgesia in the experimental setting have indeed been put forward, and— contrary to Dr Ulett's statement— there is now direct evidence that in man electroacupuncture increases the level of endorphins in CSF,<sup>4</sup>this experimental evidence cannot be directly extrapolated to the clinical situation. The evidence of controlled trials, when compared with results reported for series of patients treated without any placebo control, show that, whereas the latter claim a 70% success rate, there is no advantage shown for acupuncture over placebo in controlled studies.<sup>5</sup>This suggests that clinically, pain relief attributed to acupuncture is more likely
Unsuitable reading (P. D. James)?
Authors: L E Bottiger
Journal: BMJ (1985)

he was literally, a dwarf, and his figure, on the whole, was so deformed, that a stranger could scarcely look at him without shuddering ... his body was short but of amazing bulk and was supported on limbs which, to judge from appearances, were quite inadequate for their burden.To the huge head which reposed on his short neck."3Han d'Island is described thus: "A little man short and thick set ... his beard was red and bushy, and his head ... seemed to be thickly covered with hair of a similar colour, his mouth was large, with very thick lips; his teeth white and pointed with wide spaces between them, his nose was curved like the beak of an eagle, his grey blue eyes."'4Neither of these descriptions shows any clear, clinically recognisable details, and Quasimodo bears little physical resemblance to either; the common thread being only one of deformity.Hugo himself gives no clue in his autobiographical writings to his model for Quasimodo.No recognisable model exists in his drawings, nor is the subject mentioned in the many biographies and studies of his life and work.Did Quasimodo ever live?Victor Hugo was only 29 when Notre-Dame de Paris was published in 1831, but he had begun to consider the book as early as 1828.Until that time he had always lived in Paris, except for brief stays both in Italy and Spain with his military father.Although Hugo may have encountered some such deformed victim of Von Recklinghausen's disease while on these foreign visits, it is more likely that he encountered his model in Paris.Had such a person held any prominent position in the public life of the city when the book was published, however, he would probably have become as notorious in his time as the elephant man was many years later.The model that Hugo used for his portrayal might have been already dead when the book was published, and any person with deformities of the severity that Hugo attributes to his central character would probably have a much reduced life expectancy.Although the mystery of who it was that Hugo portrayed remains unsolved, the portrait that he made so unforgettable has incontrovertibly con- ferred upon the unfortunate subject, whoever he was, a posthumous immortality.
Dupuytren's contracture unfolded
Authors: W A Townley, R Baker, N Sheppard, A O Grobbelaar
Journal: BMJ (2006)

Dupuytren's disease is a common and disabling fibroproliferative condition of the hand.It tends to strike patients in advancing age, causing progressive digital flexion contracture.Through its many associations, Dupuytren's disease crosses all borders of medicine and is often encountered by surgeon, physician, and general practitioner alike.To the medical student, it is dependable examination fodder-a name on many lists and a sign of many systems.The early history of Dupuytren's disease lies in folklore-it has been fabled somewhat contentiously for being a disease disseminated by the Vikings, an explanation for the curling of the papal "hand of benediction," and a curse on the bagpipe craftsmanship of the MacCrimmon clan. 1 The eminent surgeon Henry Cline introduced the condition into the medical literature and carried out the first surgical corrective procedures.The French surgeon Baron Dupuytren further developed Cline's observations and cemented his reputation by providing the eponym for the condition.We have reviewed the literature with the aim of highlighting important considerations in the management of patients with Dupuytren's disease, including a succinct overview of treatment options and referral guidelines. Sources and selection criteriaWe used PubMed and Medline search engines to identify seminal reviews, studies, and trials to clarify current knowledge of Dupuytren's disease.We used broad search terms to ensure that we identified all relevant papers.We cast the net further by scouring all reference lists to ensure that we omitted no important articles.
Tuberculosis and the Health Service
Authors: L. N. Grunbaum
Journal: BMJ (1951)

Hypermobile Ehlers Danlos Syndrome (hEDS)/hypermobility spectrum disorders (HSD) are incapacitating and painful syndromes involving a generalized connective tissue disorder with joint hypermobility and musculoskeletal complications. A neuropathic component is clinically likely given frequent burning sensations, hypoesthesia, or allodynia. Small fiber neuropathy (SFN) refers to the dysfunction or damage of A-δ and C-fibers, which relay thermal and nociceptive information as well as mediating autonomic function. SFN has been suggested by prior studies in hEDS but these early findings (case series N≤20) with sole reliance on intraepidermal nerve fiber density (IENFD) called for a larger sample combined with functional testing. In this retrospective chart extraction from 79 hEDS/HSD patients referred to a pain center due to neuropathic pain or dysautonomia, both functional (Quantitative Sensory Testing (QST), N=79) and structural (IENFD, N=69) evaluations of small nerve fibers were analyzed in combination with clinical data and standardized questionnaires. All the patients reported moderate to severe pain interfering with daily life. A decreased thermal detection (QST) was shown in 55/79 patients (70%) and a decreased IENFD in 54/69 patients (78%). Hence a small fiber neuropathy (both abnormal IENFD and QST) was definite in 40/69 patients (58%), possible in 23/69 patients (33%) and excluded in only 6/69 patients (9%). These results add strong evidence for a peripheral neuropathic contribution to pain symptoms in hEDS/HSD, in addition to the known nociceptive and central sensitization components. Such neuropathic contribution could raise the hypothesis of a neurological cause of hEDS, the only EDS syndrome still without a known genetic cause. Hence, our data is leading the way to a better stratification of this very heterogeneous population, which could improve symptom management and expand pathophysiological research.
Clichés of Nursing Education
Authors: Thomas Hale
Journal: New England Journal of Medicine (1968)

THE concerted drive of nurse educationists and nursing organizations to abolish hospital schools of nursing and practical-nurse schools comes to a head at a time when the shortage of bedside nurses throughout the country has finally reached the proportions of a national scandal and gives every indication of getting worse each year. Although 439 more nurses were graduated in 1965–66 than in 1964–65,1 this is hardly a drop in the bucket compared to the rapidly expanding needs. An increment of many thousands of nurses each year is needed, not only to make up the current deficit but also to allow . . .