tbuckley/cabot-search huggingface dataset:
Abstract 160: Targeting cysteine-mediated dimerization of the MUC1-C oncoprotein in human cancer cells
Authors: Deepak Raina, Rehan Ahmad, Hasan Rajabi, Govind Panchamoorthy, Donald W. Kufe, Surender Kharbanda
Journal: Cancer Research (2012)

Abstract The MUC1 heterodimeric protein is aberrantly overexpressed in diverse human carcinomas and contributes to the malignant phenotype. The MUC1-C transmembrane subunit contains a CQC motif in the cytoplasmic domain that has been implicated in the formation of dimers and in its oncogenic function. The present studies demonstrate that MUC1-C forms dimers in human breast and lung cancer cells. MUC1-C dimerization was detectable in the cytoplasm and was independent of MUC1-N, the N-terminal mucin subunit that extends outside the cell. We show that the MUC1-C cytoplasmic domain forms dimers in vitro that are disrupted by reducing agents. Moreover, dimerization of the MUC1-C subunit in cancer cells was blocked by reducing agents and increased by oxidative stress, supporting involvement of the CQC motif in forming disulfide bonds. In support of these observations, mutation of the MUC1-C CQC motif to AQA completely blocked MUC1-C dimerization. Importantly, these studies were performed with MUC1-C devoid of fluorescent proteins, such as GFP, CFP and YFP. In this regard, we show that GFP, CFP and YFP themselves form dimers that are readily detectable with cross-linking agents. The present results further demonstrate that a cell-penetrating peptide that targets the MUC1-C CQC cysteines blocks MUC1-C dimerization in cancer cells. These findings provide definitive evidence that (i) the MUC1-C cytoplasmic domain cysteines are necessary and sufficient for MUC1-C dimerization and (ii) these CQC motif cysteine represent an Achilles’ heel for targeting MUC1-C function. 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 160. doi:1538-7445.AM2012-160
Immunoglobulin Responses in Rubella and its Complications
Authors: M. Haire, D. S. M. Hadden
Journal: BMJ (1970)

Normal responses of rubella-specific IgG and IgM antibody were assessed in eight patient by immunofluorescence. A prolonged rubella-specific IgM response was shown in three patients with complications of rubella infection. Two patients had thrombocytopenic purpura and one had carpal-tunnel compression.
Treatment of spinal osteoporosis in postmenopausal women.
Authors: B E Nordin, A Horsman, R G Crilly, D H Marshall, M Simpson
Journal: BMJ (1980)

Ninety-five postmenopausal women with unequivocably wedged or compressed vertebrae in whom the recognised causes of secondary osteoporosis had been excluded were studied, 41 having no treatment and the rest one or more of six different treatments. The treatment regimens comprised calcium supplements, vitamin D, calcium and vitamin D, ethinyloestradiol or--where oestrogens were contraindicated--norethisterone, 1 alpha-hydroxycholecalciferol (1 alpha-OHD3), or hormones with 1 alpha-OHD3. The seven groups were reasonably comparable in most respects except that the hormone-treated patients were younger and had a higher initial cortical area ratio than the others, and the calcium- and hormone-treated groups had the best initial radio-calcium absorption. The untreated osteoporotic patients lost cortical bone more rapidly than do normal postmenopausal women. Three treatments (calcium, hormones, and 1 alpha OHD3 plus hormones) appear to be useful in modifying the disease, and two treatments (vitamin D and 1 alpha-OHD3) useless or even harmful. Vitamin D and 1 alpha-OHD3 are more safely used in conjunction with oestrogens, which protect bone against resorption, than on their own.
EMOTIONS AND BIOCHEMICAL FINDINGS IN ALCOHOLISM
Authors: M. FREILE FLEETWOOD, OSKAR DIETHELM
Journal: American Journal of Psychiatry (1951)

In a combined psychiatric-biochemical study of patients suffering from chronic alcoholism, emotions were determined by one investigator (O.D.) and biochemical studies were carried out simultaneously by the other (M.F.F.). In anxiety the biochemical substance is apparently nor-epinephrine, while in tension cholinergic substances are present. The substance found in the presence of resentment cannot be defined, but it is definitely not acetylcholine. It was found that the alcoholic patients had varying degrees of resentment when an urge to drink was present. Alcohol relieved the resentment and the corresponding substance in the blood disappeared. In a few patients, tension and correlated biochemical substances were also present and were affected by alcohol. Anxiety was somewhat decreased but not completely abolished. There are no indications that the resentment in alcoholic patients is different from that presented by other subjects.
MPs call for Lansley to publish risk register of NHS shake up
Authors: C. Dyer
Journal: BMJ (2012)

Pressure is mounting on the health secretary for England, Andrew Lansley, to release the confidential strategic risk register drawn up by his department outlining the dangers posed by his controversial shake-up of the National Health Service.

Fifty MPs including nine Liberal Democrats, whose party is the minority party in the coalition government, have signed an early day motion demanding release of the register. And Labour is to hold an opposition day debate later this month calling on the health secretary to publish it.

Following Freedom of Information Act requests by the London Evening Standard newspaper and by former Labour health spokesman John Healey, Mr Lansley was ordered last November by the information commissioner, Christopher Graham, to make the document public ( BMJ 2011;343, d7404, doi:10.1136/bmj.d7407). But the health secretary elected instead to appeal to the …
Propranolol-induced depression.
Authors: J. D. Fitzgerald
Journal: BMJ (1967)

Death from Exposure SIR,-Many mountaineering deaths are put down as being due to " exposure," either alone or in conjunction with injuries.These unfortunate people are often diagnosed as being dead by lay people on the hill, and treated accordingly-that is, head covered, often by plastic or similar impervious material.Perhaps, therefore, it would be wise to emphasize the difficulties of diagnosing death in a patient suffering from hypo- thermia.Mountain Rescue Figures in 1961-5 for Great Britain
The First Strictly Full-time Professor of Medicine in an American Medical School: Hopkins, Not Michigan
Authors: Allen B. Weisse
Journal: JAMA (1991)

<h3>To the Editor.</h3> — I enjoyed another of Dr Fye's<sup>1</sup>enlightening articles on American medical history but was jarred by the implication that Theodore C. Janeway was the first full-time chairman of medicine in the United States when he was appointed to that position at The Johns Hopkins Hospital, Baltimore, Md. My old mentor, William Dock, was rarely wrong about anything, a fact of which you could be reminded often in his charming, disarming, and utterly truthful way. One of his claims was that his father, George Dock, was the first full-time chairman of medicine in this country when he assumed the chair at the University of Michigan, Ann Arbor.<sup>2</sup>Following my reading of the Fye article, I checked with Michigan historian Dr Joel D. Howell, who referred me to Horace Davenport's book of the school, which indicated Dock's appointment in 1891.<sup>3</sup> Janeway accepted the chair at
Dilatation of Left Ventricular Cavity on Stress Thallium Scan as an Indicator of Ischemic Disease
Authors: JERRY STOLZENBERG
Journal: Clinical Nuclear Medicine (1980)

The left ventricular cavity seen on a stress thallium scan is normally smaller than that on a non-stress scan. This size differential can be used as an adjunct in the interpretation of borderline relative changes in perfusion seen in coronary artery disease or in the elimination of some false-negatives secondary to balanced lesions.
Synergistic Activity of PARP Inhibition by Talazoparib (BMN 673) with Temozolomide in Pediatric Cancer Models in the Pediatric Preclinical Testing Program
Authors: Malcolm A. Smith, C. Patrick Reynolds, Min H. Kang, E. Anders Kolb, Richard Gorlick, Hernan Carol, Richard B. Lock, Stephen T. Keir, John M. Maris, Catherine A. Billups, Dmitry Lyalin, Raushan T. Kurmasheva, Peter J. Houghton
Journal: Clinical Cancer Research (2014)

Abstract Purpose: Inhibitors of PARP, an enzyme involved in base excision repair, have demonstrated single-agent activity against tumors deficient in homologous repair processes. Ewing sarcoma cells are also sensitive to PARP inhibitors, although the mechanism is not understood. Here, we evaluated the stereo-selective PARP inhibitor, talazoparib (BMN 673), combined with temozolomide or topotecan. Experimental Design: Talazoparib was tested in vitro in combination with temozolomide (0.3–1,000 μmol/L) or topotecan (0.03–100 nmol/L) and in vivo at a dose of 0.1 mg/kg administered twice daily for 5 days combined with temozolomide (30 mg/kg/daily x 5; combination A) or 0.25 mg/kg administered twice daily for 5 days combined with temozolomide (12 mg/kg/daily x 5; combination B). Pharmacodynamic studies were undertaken after 1 or 5 days of treatment. Results: In vitro talazoparib potentiated the toxicity of temozolomide up to 85-fold, with marked potentiation in Ewing sarcoma and leukemia lines (30–50-fold). There was less potentiation for topotecan. In vivo, talazoparib potentiated the toxicity of temozolomide, and combination A and combination B represent the MTDs when combined with low-dose or high-dose talazoparib, respectively. Both combinations demonstrated significant synergism against 5 of 10 Ewing sarcoma xenografts. The combination demonstrated modest activity against most other xenograft models. Pharmacodynamic studies showed a treatment-induced complete loss of PARP only in tumor models sensitive to either talazoparib alone or talazoparib plus temozolomide. Conclusions: The high level of activity observed for talazoparib plus temozolomide in Ewing sarcoma xenografts makes this an interesting combination to consider for pediatric evaluation. Clin Cancer Res; 21(4); 819–32. ©2014 AACR.
Critical Care Medicine Handbook
Authors: Lawrence L. Hirsch
Journal: JAMA (1976)

Although containing some features of a handbook, this publication is an unusual report of the proceedings of a symposium on critical care medicine. Sixty-nine presentations are, with one exception, reduced to a median of five pages each. The various authors have done an outstanding job in emphasizing the "why" and "how" of treating specific respiratory, cardiovascular, central nervous system, gastrointestinal, and endocrine crises. In addition, there are worthwhile articles on trauma, fluids and electrolytes, infection, and a miscellaneous group labeled "Special Problems." Much of the material is quite new. Just a few examples will illustrate the fine quality of this volume: De Angelis presents a practical analysis of "Endotracheal Intubation vs Tracheostomy" in six pages and four sets of clear illustrations; Schumer's "Shock as a Syndrome of Metabolic Failure" is a superbly lucid and simple biochemical explanation in a mere four pages; Guntheroth, in only six pages, lays down the
Foreign-born Medical Colleagues
Authors: Bruce R. Holzman
Journal: JAMA (1978)

To the Editor.—  In his commentary A Prescription for the Rising Cost of Medical Care (237:2383-2384, 1977), Vernon H. Mark, MD, states that all too often, when they finish their educational program, they enter the  medical system in areas where they are least needed.  quote is in reference to the ever increasing number of foreign-born medical graduates (FBMGs) who are swelling the physicians' ranks in this country. Even if this allegation is correct, in part or whole, Dr Mark's proposed solution to this problem is wrong both in principle and practice. He proposes to limit the FBMG to two years postgraduate training in this country: This would prevent them from becoming Boardcertified and theoretically discourage their entry into the American medical system.  In his aside concerning the surgical and medical specialties as well as elsewhere in his commentary, he favors simple solutions for complex problems. The problems he
The natural history of nonalcoholic fatty liver disease with advanced fibrosis or cirrhosis: An international collaborative study
Authors: Neeraj Bhala, Paul Angulo, David van der Poorten, Eric Lee, Jason M. Hui, Giorgio Saracco, Leon A. Adams, Phunchai Charatcharoenwitthaya, Joanne H. Topping, Elisabetta Bugianesi, Christopher P. Day, Jacob George
Journal: Hepatology (2011)

Information on the long-term prognosis of nonalcoholic fatty liver disease (NAFLD) is limited. We sought to describe the long-term morbidity and mortality of patients with NAFLD with advanced fibrosis or cirrhosis by prospectively studying 247 such patients from four international centers (in Australia, USA, UK and Italy). Their natural history was then compared with 264 patients with HCV infection who were either naïve or non-responders to treatment. Both cohorts were Child-Pugh class A and had advanced fibrosis (stage 3) or cirrhosis (stage 4) confirmed by liver biopsy at enrollment. In the NAFLD cohort, followed up for a mean of 85.6 months (range, 6-297), there were 48 (19.4%) liver-related complications and 33 (13.4%) deaths or liver transplants. In the HCV cohort, followed up for 74.9 months (mean; range, 6-238), there were 47 (16.7%) liver-related complications and 25 (9.4%) deaths or liver transplants. When adjusting for baseline differences in age and gender, the cumulative incidence of liver-related complications was lower in the NAFLD than the HCV cohort ( P = 0.03), including incident hepatocellular cancer (6 versus 18; P = 0.03), but that of cardiovascular events ( P = 0.17) and overall mortality ( P = 0.6) were similar in both groups. In the NAFLD cohort, platelet count, stage 4 fibrosis, lowered platelet count, and lowered serum cholesterol and alanine aminotrasferase (ALT) levels were associated with liver-related complications; an aspartate aminotransferase/ALT ratio &gt;1 and older age were associated with overall mortality, and higher serum bilirubin levels and stage 4 fibrosis were associated with liver-related mortality. Conclusions: Patients with NAFLD with advanced fibrosis or cirrhosis have lower rates of liver-related complications and hepatocellular cancer than corresponding patients with HCV infection, but similar overall mortality. Some clinical and laboratory features predict liver-related complications and other outcomes in patients with NAFLD. (Hepatology 2011;54:1208–1216)
THE CAUSES OF THE VARIATIONS OF THE CARDIOAORTIC OR “PRESPHYGMIC” INTERVAL.
Authors: A. T. KEYT
Journal: JAMA (1883)

ChapterIII. One of the outcomes of the simultaneous graphic method has been the demonstration and measurement of an interval of time between the beginning of ventricular contraction or systole and opening of the aortic valves, or beginning of the aortic pulse. The term “presphygmic,” applied to this interval by the author, appears well chosen, as expressing the phase of ventricular systole which precedes the rise of the arterial pulse. This term and “cardio-aortic/p=''/ or “ventriculo-aortic,” will be used synonymously in this article. Observations relating to the presphygmic interval must necessarily be made on man between the pointof of ventricular beat and the point of pulsation of a near artery, as the carotid, or subclavian; the former being usually selected as more accessible for exploration. To get the presphygmic interval in its purity, it is only required to deduct from the full cardio-carotid interval the brief transmission interval of the
Systemic retinoids for the chemoprevention of cutaneous squamous cell carcinoma and verrucal keratosis in a cohort of patients on BRAF inhibitors
Authors: R. Anforth, T.C.M.P. Blumetti, A. Clements, R. Kefford, G.V. Long, P. Fernandez-Peñas
Journal: British Journal of Dermatology (2013)

The treatment of metastatic melanoma has changed greatly with the development of inhibitors targeted at the mutated BRAF kinase present in up to 50% of metastatic melanoma cases. These agents, vemurafenib and dabrafenib, have been shown to increase median survival. Unfortunately, they have also been associated with the development of verrucal keratosis (VK) and cutaneous squamous cell carcinoma (cuSCC). These lesions require surgical excision, and when a large number of these lesions need to be treated, it can significantly affect the patient's quality of life.To determine if acitretin is suitable as a chemopreventative agent against the development of verrucal keratosis and cuSCC, in patients on BRAF inhibitors.Patients treated with a BRAF inhibitor, vemurafenib or dabrafenib, for stage IV metastatic melanoma, who had undergone more than five surgical excisions to remove lesions suggestive of cuSCC, were offered the opportunity to commence acitretin as a chemopreventative agent. Patients were evaluated every 4 weeks. Clinical and histological data were collected.Eight patients, who had a total of 24 cuSCC removed, were included in the study. After commencement of acitretin, only five cuSCC were excised from two patients. The most significant reduction was in a patient who had developed 13 cuSCC over 10 months and only two cuSCC 3 months after commencing acitretin. No modifications in the dose of the BRAF inhibitor were made as a result of cuSCC in any of these patients.Acitretin should be considered as a chemopreventative agent for VK and cuSCC in patients taking BRAF inhibitors, before considering dosage reductions.
Patient Consent for Publication
Authors: Renée Ridzon
Journal: JAMA (1997)

<h3>To the Editor.</h3> —We are authors of the manuscript submitted to JAMA that reported an outbreak of drug-resistant tuberculosis referred to by Dr Snider in his article.<sup>1</sup>The case reports in our manuscript contain no identifying information; even age and sex are omitted because of their limited relevance to that report. Rejected by<i>JAMA</i>, the same manuscript was subsequently accepted for publication (with case reports) in another peer-reviewed journal<sup>2</sup>; this journal did not require patient consent. We have recently published other case reports that have contained sensitive information without requests from the editors for patient consent.<sup>3-5</sup>Of note, one of these journals is represented in the ICMJE. In one of the manuscripts accepted for publication, the picture and name of a patient described in a case report had appeared in a major newspaper prior to publication of the manuscript.<sup>4</sup>With regard to the outbreak of drug-resistant tuberculosis,<sup>2</sup>because
EARLY PULMONARY LESIONS IN PARTIALLY IMMUNE ALCOHOLIZED MICE FOLLOWING INHALATION OF VIRULENT PNEUMOCOCCI
Authors: Ernest G. Stillman, Arnold Branch
Journal: The Journal of Experimental Medicine (1930)

1. The serial section examination of 71 partially immune alcoholised mice which were killed at intervals following the inhalation of virulent pneumococci showed pulmonary localisation in 7 or 9%. 2. In the case of the mouse the initial lesion of pneumococcus pneumonia is in the alveolar wall and the exudate into the alveolar lumen occurs secondarily.
Self-assembled nanoparticles based on glycol chitosan bearing hydrophobic moieties as carriers for doxorubicin: In vivo biodistribution and anti-tumor activity
Authors: Jae Hyung Park, Seunglee Kwon, Minsu Lee, Hesson Chung, Ji-Hyun Kim, Yoo-Shin Kim, Rang-Woon Park, In-San Kim, Sang Bong Seo, Ick Chan Kwon, Seo Young Jeong
Journal: Biomaterials (2005)
Reducing Falls Among Patients in Nursing Homes
Authors: James W. Cooper
Journal: JAMA (1997)

To the Editor.  —In the article on reducing falls in nursing homes by Dr Ray and colleagues,1the context section of the abstract indicates that  interventions have been shown to prevent falls in nursing home residents.... However, at least 2 studies2,3have demonstrated that decreasing the use of psychoactive medications, and psychotropic agents in particular, reduces falls and fall-related injuries.  One study2has shown that consultation with recommendations to limit shorter-acting benzodiazepines to no more than 3 doses per week and reduce the dose of triazolam from 250 to 125 pg reduced the occurrence of falls from 4 to none in 7 patients over a 1-year period. In a subsequent 1-year study of 182 patients, 54% of whom fell an average of 2.9 times, consultant pharmacist intervention determined that medications contributed to 85% offalls.3Psychotropic agents, other psychoactive drugs, and antihypertensive medications were the most
Extended distribution of prolonged and fractionated right atrial electrograms predicts the development of chronic atrial fibrillation in patients with idiopathic paroxysmal atrial fibrillation
Authors: Kojiro Nakao, Shinji Seto, Chiaki Ueyama, Kiyotaka Matsuo, Norihiro Komiya, Shojiro Isomoto, Motonobu Hayano, Katsusuke Yano
Journal: Journal of the American College of Cardiology (2002)
Atlas of Sodium Fluoride PET Bone Scans
Authors: Sindu Sheth, Patrick M. Colletti
Journal: Clinical Nuclear Medicine (2012)

Sodium fluoride (NaF) is a bone-seeking positron-emitting tracer with high sensitivity and specificity for detection of osseous lesions, particularly osteolytic lesions. We believe that NaF positron emission tomography (PET)/computed tomography (CT) scans can provide a more thorough and conclusive evaluation of bone diseases than conventional Technetium-99m-methylene diphosphonate bone scans. Understanding both normal and pathologic patterns is important for the evaluation and interpretation of these studies. Thus, an atlas of NaF positron emission tomography/computed tomography bone scans demonstrating benign, pathologic, and malignant osseous lesions as well as extraosseous lesions will be invaluable in the correct interpretation and diagnosis of osseous lesions.
<i>Chlamydia psittaci</i>— Reemergence of a Forgotten Pathogen
Authors: Julius Schachter
Journal: New England Journal of Medicine (1986)

The genus chlamydia consists of two species, psittaci and trachomatis. C. psittaci attracted attention during a pandemic in 1929–1930, when it was shown to cause psittacosis ("parrot fever," from the Greek word psittakos, "parrot").1 Exotic birds are not the only source of human infections, however. C. psittaci has been recovered from more than 130 avian species and is also an important pathogen among domestic mammals. Psittacosis is an occupational hazard to workers in the poultry industry.Psittacosis is considered to be exclusively a zoonosis; person-to-person transmission can occur but is rare. Some cases of psittacosis involve no known avian . . .