tbuckley/cabot-search huggingface dataset:
Abstract 261: Emerging roles for the CREB regulated transcription coactivators (CRTCs) in oncogenesis
Authors: Antonio L. Amelio, Frank C. Dorsey, Meredith A. Steeves, Mark R. Southern, Brandon M. Young, Mariam B. Lawani, Stephanie M. Prater, Adam S. Alperstein, John L. Cleveland, Michael D. Conkright
Journal: Cancer Research (2011)

Abstract Oncogenesis is a complex, multi-factorial process of cellular transformation that leads to the development of many types of cancers. The factors that contribute to this process reprogram normal cellular functions, including metabolic pathways, and allow uncontrolled cell growth. The CRTC family of CREB coactivators, in conjunction with CBP/p300, cooperate in the regulation of cAMP-inducible genes involved in cell survival, proliferation, glucose metabolism, and adaptive mitochondrial biogenesis. A subset of tumors share a common t(11;19)(q21;p13.1) translocation that forms a chimeric oncogene by fusing CRTC1 to the NOTCH coactivator MAML2. Consequently, the CRTC1/MAML2 translocation induces the aberrant expression of genes regulated by CREB and NOTCH and the deregulation of these target genes is believed to cause tumorigenesis. We demonstrate that a gain-of-function activity by the CRTC1/MAML2 oncoprotein promotes interactions with the MYC:MAX network. This interaction is specific as neither CRTC1 or MAML2 parental proteins activate MYC:MAX complexes. Specifically, RNA-seq analysis revealed that a significant proporation of genes involved in key aspects of cell growth, survival, and metabolism within the MYC:MAX and CREB transcription networks are induced by CRTC1/MAML2. Analysis of cellular transformation by RK3E foci formation assays identified a synergistic effect of MYC expression on CRTC1/MAML2-induced transformation and this can be blocked by a dominant negative MYC molecule. Furthermore, in-frame deletions of CRTC1/MAML2 that lack transforming activity are unable to induce the expression of MYC-responsive reporters revealing a critical role for MYC target genes in CRTC1/MAML2-induced cell growth and transformation. Collectively, these studies indicate that CRTC1/MAML2 promotes cellular transformation through cooperative activation of MYC and CREB pathways thereby challenging current paradigms which suggest that translocations function through aberrant activation of parental pathways. 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 261. doi:10.1158/1538-7445.AM2011-261
Tuberculosis as a Continuing Cause of Renal Amyloidosis
Authors: A. C. Kennedy, J. A. Burton, M. E. M. Allison
Journal: BMJ (1974)

In 40 patients with renal amyloidosis seen in a ten-year period tuberculosis was the major preceding disease in 20, though it was active in only two at diagnosis. Most patients presented with renal failure, and only two survived for five years. This experience (at least, in the west of Scotland) conflicts with the generally accepted view that rheumatoid arthritis is the commonest cause of renal amyloidosis.
Network that oversees cancer trials in the US needs to be streamlined, says report
Authors: S. Mayor
Journal: BMJ (2010)

The organisation and funding of clinical trials in cancer in the US needs a complete overhaul to improve their efficiency and prioritisation of research questions and to make better use of new technologies such as biomarkers, warns a report from the Institute of Medicine launched at the American Society of Clinical Oncology annual meeting in Chicago, 4 to 8 June.

The National Cancer Institute’s Clinical Trials Cooperative Group Program has taken the lead in organising clinical trials to explore new and improved cancer treatments for the past 50 years. It comprises 10 groups bringing together more than 3000 institutions, including the Cancer and Leukemia Group B, the Eastern Cooperative Group, and the Southwest Oncology Group, which have made major contributions to improving the treatment of a range of …
Deficient Serum Bactericidal Activity Against Escherichia Coli in Patients with Cirrhosis of the Liver
Authors: Joshua Fierer, Fred Finley
Journal: Journal of Clinical Investigation (1979)

The serum bactericidal activity (SBA) of cirrhotic patients was compared with that of normal individuals using the release of 51Cr from radiolabeled Escherichia coli as the assay method. 80% (22/27) of patients were found to have deficient SBA against at least one of three smooth, serum-sensitive test strains of E. coli. Cirrhotic patients were found to have normal levels of serum lysozyme. Although some patients were mildly hypocomplementemic, this abnormality did not correlate with the presence of a bactericidal defect. Bactericidal antibody in normal and cirrhotics' sera was limited to the immunoglobulin (Ig)M class. Purified IgM from patients with deficient SBA against E. coli 0111 had lower concentrations of bactericidal antibody for that E. coli than did IgM from normal sera; the calculated bactericidal activity of total serum IgM was also lower. The bactericidal defect in cirrhotic serum could be completely corrected by either human antiserum to the homologous strain of E. coli or by purified, normal human IgM. However, because higher concentrations of IgM were required to restore normal SBA to a cirrhotic's serum than to agammaglobulinemic serum, there may be an inhibitor of bactericidal antibody in addition to a deficiency of bactericidal IgM antibody to E. coli in the serum of patients with cirrhosis. The bactericidal activity of the alternative complement pathway was also assessed. Sera from cirrhotic patients had no deficit in SBA attributable to the alternative complement pathway. In fact, in some, the activity of the alternative complement pathway was supernormal, compensating in part for the deficit in IgM-mediated SBA.
Actual causes of death in the United States
Authors: J. E. Lincoln
Journal: JAMA (1994)

To the Editor.  —If cigarette smoking is as lethal as authorities continue to say it is, 1 why have the experimental outcomes of randomized intervention trials 2-5 failed to date to indicate (by generating greater mortality rate reductions among baseline-defined smokers than among baseline-defined nonsmokers) that successful smoking cessation guidance prolongs survival? How can the outstanding longevity of Japanese men be reconciled with a smoking prevalence among them that is higher than for most other countries? Why is the approximate 4.6:1 ratio of male-to-female cigarette smoking prevalence for Japan, vs only about 1.3:1 for the United States, not reflected in a wider gap between men's and women's life expectancy for the Japanese than for the Americans?  Financial Disclosure.  —Mr Lincoln has about 20% of his pension under the control of Philip Morris, and about 15% of his net worth is in tobacco company securities.
The recognition of childhood thyroid cancer as a consequence of the Chernobyl accident: an allegorical tale of our time?
Authors: K. Baverstock
Journal: Journal of the Royal Society of Medicine (2007)

I begin with something said by the physicist Edward Lorenz: ‘let our premise be that we should believe what is true even if it hurts, rather than what is false even if that makes us happy’.1 Lorenz is often called the ‘father of chaos’, since he was the first to note that some complex dynamic systems had an exquisitely sensitive dependence on ‘initial conditions’. This meant that their evolution could not be predicted over long periods of time. The weather is one of those systems. He made the above statement in the context of discussing whether humans truly have free will, but I have found another context in which it is equally applicable: I think it a very relevant observation on how human nature is able to believe something even in the face of overwhelming evidence to the contrary.

In this paper I illustrate how an important truth emerged from the chaos of the Chernobyl accident over the period 1992-1998, and what factors might have influenced this process; I ask whether there are any lessons to be learnt from this experience; and finally I suggest five truths that I discern from the accident and its consequences.
Mapping interactions between complement C3 and regulators using mutations in atypical hemolytic uremic syndrome
Authors: Elizabeth C. Schramm, Lubka T. Roumenina, Tania Rybkine, Sophie Chauvet, Paula Vieira-Martins, Christophe Hue, Tara Maga, Elisabetta Valoti, Valerie Wilson, Sakari Jokiranta, Richard J. H. Smith, Marina Noris, Tim Goodship, John P. Atkinson, Veronique Fremeaux-Bacchi
Journal: Blood (2015)
Complications of Determining the Central Venous Pressure
Authors: Robert Matz
Journal: New England Journal of Medicine (1965)

WITHIN the space of one week 6 cases of an avoidable "disease of medical progress" have been encountered. The advantages of determining the central as opposed to the peripheral venous pressure have been adequately stressed in the recent medical literature.1 Although many methods of determining the central venous pressure are feasible the one utilized by most of the house officers at this institution is that of percutaneous puncture of the subclavian vein, with introduction of a large-bore (No. 14 or 17) Bardic Intracath into the superior vena cava.Case ReportsCase 1. A patient who had had a resection of . . .
Contrasting Effects of Conjugated Estrogens and Tamoxifen on Dilator Responses of Atherosclerotic Epicardial Coronary Arteries in Nonhuman Primates
Authors: J. Koudy Williams, Erika K. Honoré, Michael R. Adams
Journal: Circulation (1997)

Background Estrogens have been shown to improve dilator responses of atherosclerotic coronary arteries. Tamoxifen is a mixed estrogen agonist/antagonist with as yet unexplored effects on vascular function. Therefore, the goal of this study was to compare the effects of conjugated equine estrogens (CEEs) with those of tamoxifen on epicardial coronary artery dilator responses in atherosclerotic, ovariectomized monkeys. Methods and Results Fifty ovariectomized cynomolgus monkeys were fed an atherogenic diet for 34 months. During this time, monkeys were assigned to one of three treatment groups: (1) control, no hormone replacement (n=15); (2) CEEs mixed in the diet at a dose of 0.043 mg · kg −1 · d −1 (n=14); or (3) tamoxifen mixed in the diet at a dose of 1.3 mg · kg −1 · d −1 (n=21). Quantitative angiography was used to measure coronary artery dilator responses to intracoronary infusions of acetylcholine (10 −8 , 10 −7 , and 10 −6 mol/L) and nitroglycerin (15 μg/min). Coronary arteries of the tamoxifen-treated group constricted in response to high-dose acetylcholine (−5.4± 2.3%, P &lt;.05 versus control), whereas those of the CEE group did not ( P &gt;.05 versus control). Conversely, arteries from the CEE group dilated in response to nitroglycerin (9.1±2.1%, P &lt;.05 versus control), whereas those from the tamoxifen group did not ( P &gt;.05 versus control). Statistical adjustments for variations in plaque extent (determined subsequently after necropsy) and plasma lipoproteins did not alter the results. Conclusions Tamoxifen has primarily estrogen-antagonistic effects on epicardial coronary artery dilator responses in atherosclerotic monkeys. Results implicate the estrogen receptor as a modulator of coronary artery dilator responses in ovariectomized, atherosclerotic monkeys.
Computed Tomography Findings in Acute Exacerbation of Idiopathic Pulmonary Fibrosis
Authors: Masanori Akira, Takenori Kozuka, Satoru Yamamoto, Mitsunori Sakatani
Journal: American Journal of Respiratory and Critical Care Medicine (2008)

The serial computed tomography findings and prognosis of the acute exacerbation of idiopathic pulmonary fibrosis (IPF) are not yet well defined in a larger number of cases.To evaluate the parenchymal abnormalities and prognosis using high-resolution computed tomography (HRCT) in acute exacerbation of IPF.The study consisted of clinical, laboratory, and HRCT data before and at the time of acute exacerbation in 64 episodes of 58 patients with IPF. A semiquantitative analysis of overall extent of parenchymal abnormalities, extent of alveolar opacity (ground-glass attenuation and consolidation), and extent of fibrotic opacity (reticulation and honeycombing) on CT was performed by two chest radiologists. The newly appeared parenchymal abnormalities were also classified into three patterns: peripheral, multifocal, and diffuse.In all patients, HRCT scans taken at the exacerbation showed typical signs of IPF and newly developing alveolar opacity. They included 34 patients of peripheral pattern, 8 of multifocal pattern, and 16 of diffuse pattern. Twenty-five patients died and 33 survived after the initial exacerbation. Worse survival was associated with patients with diffuse type compared with patients with multifocal and peripheral type. The CT patterns and overall CT extent were associated with an increased hazard of death after adjusting for age, sex, smoking, baseline diffusion capacity for carbon monoxide, baseline FVC, and disease extent on CT. On multivariate analysis, the strongest correlations were observed between CT patterns (combined diffuse and multifocal versus peripheral) and survival (odds ratio, 4.629; 95% confidence interval, 1.900-11.278; P = 0.001).HRCT extent and patterns are predictive of survival in acute exacerbation of IPF.
Ambulatory continuous positive airway pressure without polysomnography in patients with a high probability of obstructive sleep apnoea
Authors: Veronica Smith
Journal: Thorax (2007)

▴ Mulgrew AT, Fox N, Ayas NT, et al . Diagnosis and initial management of obstructive sleep apnea without polysomnography. A randomized validation study. Ann Int Med2007;146:157–6.

[OpenUrl][1][PubMed][2][Web of Science][3]



Obstructive sleep apnoea (OSA) is a common condition, diagnosed by polysomnography. However, polysomnography is costly and its availability often limited, leading to a delay in diagnosis and initiation of treatment in OSA.

This randomised, controlled study compared the use of polysomnography for the diagnosis of OSA with …

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Euglycaemic Diabetic Ketoacidosis
Authors: J. F. Munro, I. W. Campbell, A. C. McCuish, L. J. P. Duncan
Journal: BMJ (1973)

Of a series of 211 episodes of diabetic metabolic decompensation 37 had severe euglycaemic ketoacidosis (a blood sugar level of less than 300 mg/100 ml and a plasma bicarbonate of 10 mEq/1. or less). All were young insulin-dependent diabetics, only one being previously undiagnosed. Vomiting was a common factor, and in all carbohydrate reduction occurred with continued or increased daily insulin dose. Treatment comprised fluid and electrolyte replacement and large doses of insulin covered by adequate carbohydrate, many receiving 10% dextrose. Alkali was either withheld or given sparingly and the therapy was monitored by serial estimations of plasma bicarbonate. All the patients survived.
William David Smith
Authors: John Anderton, John Ridyard, Roger Fletcher
Journal: BMJ (2004)

Former consultant anaesthetist Manchester Royal Infirmary (b 1945; q Liverpool 1968; FFARCS), d 23 April 2004.​2004.




Figure 1




Bill Smith started his anaesthetic career in Preston in 1969. He became a registrar first at Withington and later at Wythenshawe hospitals in Manchester, and a consultant at Manchester Royal Infirmary in 1976. His appointment was unusual in that it specified an interest in ear, nose, and throat anaesthesia. Over the years he developed the special skills required for major head and neck surgery, oesophageal surgery, and also paediatric ENT surgery. He also made important contributions to the management of severe pre-eclampsia. Bill was a lover of classical music, in particular of singing. In the last few years of his career, he struggled with increasing disability from Parkinson's disease, taking early retirement in 1995. He leaves a wife, Gina; and two children.
Words Eaten and Lead Poisoning
Authors: Hugh H. Hussey
Journal: JAMA (1976)

<h3>To the Editor.—</h3> In response to the editorial, "Geophagia-Induced Hyperkalemia" (234:746, 1975), Margaret O'Rourke, librarian at the Rees-Stealy Medical Clinic in San Diego, wrote, "Words eaten can also be harmful. I sometimes wonder if anything is innocuous." She thoughtfully enclosed a reprint of "Lead Poisoning from Colored Printing Inks" (<i>Clinical Pediatrics</i>12:654-655, 1973) in which Hankin et al wrote Lead contained in colored pages of magazines may endanger children with pica. The lead in magazines ranged from 8 ppm for black and white pages to 3,600 ppm (0.36%) for colored pages.
Children From Romania: Testing for Tuberculosis
Authors: Mark G. Jameson
Journal: JAMA (1993)

<h3>To the Editor.</h3> —The recent article by Johnson et al<sup>1</sup>presented an excellent overview of the health of children adopted from Romania. As a physician who staffs a tuberculosis clinic that has treated a number of children from Romania, I would like to elaborate on the detection and treatment of tuberculosis discussed in the article. The authors report that 65 children participated in the study. While 61 (94%) were screened for parasites and 58 (89%) were screened for hepatitis B, only 41 (63%) were screened for tuberculosis with a purified protein derivative (PPD). In 1991, foreign-born persons accounted for 26% of the active tuberculosis cases in the United States.<sup>2</sup>A majority of foreign-born persons who develop tuberculosis do so within the first 5 years after they enter the United States.<sup>3</sup>Thus, screening of all these persons for tuberculosis on entry to the United States is important. In
Predictors of ratio of placental weight to fetal weight in multiethnic community
Authors: I. J Perry, D G Beevers, P H Whincup, D Bareford
Journal: BMJ (1995)

<h3>Abstract</h3> <b>Objective</b>: To determine whether placental ratio is influenced by maternal ethnic origin, obesity, hypertension, and haematological indices of iron deficiency anaemia. <b>Design</b>: Observational study. <b>Setting</b>: District general hospital in Birmingham. <b>Subjects</b>: 692 healthy nulliparous pregnant women, of whom 367 were European, 213 Asian, 99 Afro-Caribbean, and 13 of other or undocumented ethnic origin. <b>Main outcome measures</b>: Placental ratio and maternal body mass index, blood pressure, and haematological indices. <b>Results</b>: Though birth weight and placental weight were lower in Asian women than in other groups, mean placental ratio was similar in Asian (19.5% (SD 3.3%)), European (20.0% (4.0%)), and Afro-Caribbean women (20.4% (5.3%)). Gestational age at birth was the main predictor of placental ratio in the univariate analysis (r= -0.34, P&lt;0.001) and multivariate analysis. The only other significant predictor of placental ratio in multivariate analysis was maternal body mass index, which was positively associated with placental ratio (r=0.1, P=0.01). Mean (SD) placental ratio was not significantly higher in women who developed gestational hypertension (20.4% (4.5%)) and pre-eclampsia (23.3% (7.3%)) than in normal women (19.8% (3.8%)). No evidence of a relation between placental ratio and first antenatal visit haemoglobin concentration or mean cell volume was detected, and placental ratio was not associated with change in mean cell volume during pregnancy or with third trimester serum ferritin concentration. <b>Conclusions</b>: These data do not support the proposed association between poor maternal nutrition and increased placental ratio. The association between high placental ratio and adult hypertension may be confounded by genetic and environmental factors associated with maternal obesity (and possibly maternal hypertension). <h3>Key messages</h3> Key messages Poor maternal nutrition has been suggested as a determinant of placental ratio, and an association with haematological indices of iron deficiency anaemia has been described In this study of European, Asian, and Afro-Caribbean pregnant women placental ratio was increased in the offspring of obese women Placental ratio was not significantly associated with first antenatal visit haemoglobin concentrations or mean cell volume, change in mean cell volume between the first antenatal visit and the third trimester, or third trimester serum ferritin concentration These findings do not support the hypothesis that raised placental ratio is a marker for poor maternal nutrition
Operative Neurosurgical Techniques: Indications, Methods, and Results
Authors: Oscar Sugar
Journal: JAMA (1984)

More than 200 authors have contributed to this massive work of 94 chapters primarily devoted to indications for operations, intraoperative considerations, technical details, and results of these techniques. It represents a modernization and considerable expansion of the earlier<i>Current Techniques in Operative Neurosurgery</i>. In a number of places, alternative procedures are described, but by no means are all of them included. For instance, Cloward's operation for anterior cervical diskectomy is omitted in favor of that of Smith and Robinson. Some chapters have no illustrations at all (eg, Robinson's chapter on approaches to the cervical spine, Clark's chapter on the occipital tentorial approach to the pineal region, and Patterson's chapter on arteriovenous malformations) but most are amply illustrated, often in great detail. The list of authors includes a number well recognized in the subspecialties of which they write. Included are specialists in anesthesiology, instrumental technology, ophthalmology, orthopedic surgery, otolaryngology, plastic surgery,
Abnormal Regulation of Circulating 25-Hydroxyvitamin D in the Williams Syndrome
Authors: Ashby B. Taylor, Paula H. Stern, Norman H. Bell
Journal: New England Journal of Medicine (1982)

THE Williams syndrome is characterized by the triad supravalvular aortic stenosis, mental retardation, and an elfin facies.1 , 2 In addition, mild microcephaly, neurologic dysfunction, hallux valgus, hernias, pectus excavatum, and other congenital cardiac and vascular defects may be present. The unique facies is characterized by a medial eyebrow flare, short palpebral fissures, ocular hypotelorism, a depressed nasal bridge, periorbital fullness, strabismus, blue eyes, a stellate pattern in the iris, prominent lips, and molar hyperplasia.2 The syndrome is often associated with idiopathic hypercalcemia of infancy, which usually occurs in the first year of life.3 4 5 6 7 8 9 10 11 Patients have increased sensitivity to vitamin D.5 , 6 Balance . . .
Diagnosis and evaluation of febrile infants under 4 months of age in Japan by using RT-PCR for enterovirus
Authors: Hisashi Kawashima, Kusukazu Kobayashi, Kentarou Aritaki, Takeshi Takami, Hiroaki Ioi, Yasuyo Kashiwagi, Kouji Takekuma, Akinori Hoshika
Journal: Journal of Infection (2005)