tbuckley/cabot-search huggingface dataset:
Abstract 1594: Targeting UBP43 for repression destabilizes PML/RARα and inhibits acute promyelocytic leukemia growth
Authors: Yongli Guo, Andrey Dolinko, Fadzai Chinyengetere, Jennifer Bomberger, Robert Gallagher, Tian Ma, Fabrizio Galimberti, Xi Liu, David Sekula, Alexander Busch, Sarah Freemantle, Ethan Dmitrovsky
Journal: Cancer Research (2010)

Abstract All-trans-retinoic acid (RA) successfully treats acute promyelocytic leukemia (APL) at least partly through triggering degradation of the PML/RARα translocation product. Prior work revealed that the E1-like ubiquitin-activating enzyme (UBE1L) associates with the interferon-stimulated gene 15 (ISG15) to repress PML/RARα protein expression. The ubiquitin protease 43 (UBP43) removes ISG15 from conjugated proteins. We derived two different anti-human UBP43 antisera to examine UBP43 protein expression. This study explored whether RA regulates UBP43 expression and if UBP43 affects PML/RARα protein stability as well as growth or apoptosis of APL cells. Retinoid regulation of the UBE1L-ISG15-UBP43 pathway was studied in cultured NB4 APL cells, transgenic APL mice and leukemic cells harvested from APL patients. Whether the deconjugase UBP43 was a therapeutic target was determined through gain and loss of UBP43 expression experiments. This study extends prior work by reporting that RA-treatment induced UBP43 expression in RA-sensitive, but not in RA-resistant NB4 APL cells. This followed an induction of UBE1L and ISG15 expression in RA-sensitive APL cells. UBP43 functions as a negative feedback loop by reversing ISG15 conjugation of PML/RARα protein. Deregulating this loop by UBP43 knock-down repressed APL cell growth by further destabilizing the PML domain of PML/RARα protein. Notably, this triggered apoptosis in APL cells. In contrast, UBP43 over-expression stabilized PML/RARα protein and promoted APL cell growth by inhibiting apoptosis. RA-treatment of a murine transgenic APL model and of de novo cultures of APL cells from patients increased UBE1L, ISG15 and UBP43 expression. Thus, this study found that the deconjugase UBP43 was retinoid regulated in NB4 APL cells as well as in leukemic cells isolated directly from APL patients and in a mouse model for APL. Oncogenic effects of PML/RARα were reversed by UBP43 knock-down, which destabilized PML/RARα protein and triggered apoptosis in APL cells. Taken together, these findings establish UBP43 as a novel molecular pharmacologic target for APL. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 1594.
Immunotherapy with cat- and dog-dander extracts III. Allergen-specific immunoglobulin responses in a 1-year double-blind placebo study
Authors: H LOWENSTEIN, V GRAFFLONNEVIG, G HEDLIN, H HEILBORN, G LILJA, K NORRLIND, K PEGELOW, B SUNDIN
Journal: Journal of Allergy and Clinical Immunology (1986)
A clinico-pathological comparison of the features characterizing the atypical or dysplastic melanocytic naevus compared with normal melanocytic naevi
Authors: J. English, R. MacKie, V. Docherty, J. Ashworth
Journal: British Journal of Dermatology (1984)

Journal Article A clinico‐pathological comparison of the features characterizing the atypical or dysplastic melanocytic naevus compared with normal melanocytic naevi Get access J. English, J. English University Department of Dermatology, Western Infirmary, Glasgow Search for other works by this author on: Oxford Academic Google Scholar R. MacKie, R. MacKie University Department of Dermatology, Western Infirmary, Glasgow Search for other works by this author on: Oxford Academic Google Scholar V. Docherty, V. Docherty University Department of Dermatology, Western Infirmary, Glasgow Search for other works by this author on: Oxford Academic Google Scholar J. Ashworth J. Ashworth University Department of Dermatology, Western Infirmary, Glasgow Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 111, Issue s26, 1 July 1984, Page 36, https://doi.org/10.1111/j.1365-2133.1984.tb05261.x Published: 01 July 1984
US healthcare spending slows but continues to outpace total economic growth
Authors: B. Roehr
Journal: BMJ (2009)

<h3>ABSTRACT</h3> The multi-component Smc5/6 complex plays a critical role in the resolution of recombination intermediates formed during mitosis and meiosis, and in the cellular response to replication stress. Using recombinant proteins, we have reconstituted a series of defined <i>S. cerevisiae</i> SMC5/6 complexes, visualised them by negative stain electron microscopy, and tested their ability to function as an ATPase. We find that only the six protein ‘holo-complex’ is capable of turning over ATP and that its activity is significantly increased by the addition of double-stranded DNA to reaction mixes. Furthermore, stimulation is wholly dependent on functional ATP-binding pockets in both Smc5 and Smc6. Importantly, we demonstrate that budding yeast Nse5/6 acts as a negative regulator of Smc5/6 ATPase activity, binding to the head-end of the complex to suppress turnover, irrespective of the DNA-bound status of the complex.
Promoting health related sport by using living lab
Authors: Paula M J Harmokivi-Saloranta, Satu Parjanen
Journal: British Journal of Sports Medicine (2010)

The purpose of this presentation is to introduce the Living Lab project. Increasing physical activity is one of the main objectives in the prevention and treatment of lifestyle-related diseases. The aim of this project is to develop new innovative services of physical activity for sedentary populations. The services of physical activity will be developed by using a Living Lab. Living Lab is a system for building a future in which real-life user-driven development and innovation will be a normal co-creation technique for new products, services and societal infrastructure. In the Living Lab development projects, the users take active part in development and innovation. The user not only supplies information to the developers but also is part of the development team, for example, generating ideas. In this project, there are 12 different user groups, for example, children, young people, adults, businessmen and unemployed. These user groups are trying to find answers to questions: ‘Why doesn't citizen go in for physical activity and what it should do that he/she would be physically active?’ Finding a solution to an everyday problem can improve the quality of life for a whole user group and at the same time act as the start of a new and successful business venture. For example, stories, essays and interviews will be used as methods. Materials will be analysed and different stories can be obtained on how to activate people to health-related sports. In addition, models will be developed that encourage people to participate in physical activities that promote health.
Limitations in Treatment of Parkinson's Disease
Authors: Robert S. Schwab
Journal: New England Journal of Medicine (1968)

The tremor and rigidity of Parkinson's disease is well known to every clinician. Beaders of this journal would usually leave the details of their complicated pathoneurophysiology to their neurologic colleagues.J. B. Carman, in this issue, has such a clear, interesting and satisfactory explanation of tremor and rigidity that all of us can enjoy and understand it. Furthermore, he points out clearly how a stereotactic destructive lesion in the healthy ventrolateral thalamus can alleviate the tremor and rigidity caused by disease farther down in the brain-stem (substantia nigra).If Parkinson's disease were only tremor and rigidity, such lesion-making might be . . .
CONDITION OF THE COMMON DUCT AFTER CHOLECYSTECTOMY
Authors: E. STARR JUDD
Journal: JAMA (1923)

As a result of the development of the surgery of the biliary tract to its present state, many problems are presenting themselves which require serious consideration. The first conception of disease of the biliary tract was associated almost entirely with gallstones, but it was soon realized that calculi were only a part of the trouble and that, in most instances, the infection is in the tissues. At first the infection was believed to be only in the walls of the gallbladder. Now it is realized that it must often Be regarded as a pan-infection, since it extends to the hepatic and pancreatic tissues. During the quiescent state of the infection it is probably present in the gallbladder in a low state of virulence, while during the active state, when the infection is manifested clinically, it not only becomes more virulent in the gallbladder, but is distributed to the other parts
An Operation for Femoral Hernia
Authors: G. D. F. McFadden
Journal: BMJ (1949)

An Operation for Femoral HerniaThe discussion on femoral hernia in the British Medical Journal of October 23 and November 6 and 13, 1948, has prompted me to describe, before I intended doing so, a method of closing the femoral canal which I have been using and which I think fulfils all the requirements of an operation for femoral hernia.,In it no foreign unabsorbable
A CASE OF AMEBIC DYSENTERY TREATED WITH EMETIN HYDROCHLORID
Authors: R. E. Cloud
Journal: JAMA (1913)

<h3>History.</h3> —S. J. G., aged 34, white, male, was born in Kentucky and moved at the age of 17 to Decatur, Ala., where he lived about ten years. From Decatur he came to Birmingham (Ensley), which has been his residence continuously for the past seven years. Eight years ago he spent a month in Houston, Tex., which single trip constitutes the extent of his travels. The present trouble began three and a half or four years ago with frequent movements of bowels (fifteen or twenty stools in twenty-four hours), straining, pain in hypogastrium and over sacrum and tenderness in epigastrium. Movements consisted mostly of blood and mucus. Attacks of this kind, more or less severe, recurred three or four times a year, usually lasting a month or more. Stools would number two or three a day during intervals between severe attacks, never being entirely free from mucus and blood and
USE OF BENZENE IN THE TREATMENT OF BURNS
Authors: Carey P. McCord
Journal: JAMA (1960)

To the Editor:—  The Journal, Nov. 17, 1959, page 1357, contains an official report of the Council on Drugs entitled Current Status of The Therapy of Burns. It is dismaying to discover that that report advocates the use of benzene in the treatment of burns. It is true that the word frugal modifies the recommendation, but the word frugal is not a quantitative term.  Of all hydrocarbons in extensive use it is probable that benzene is the most toxic. At the present time the maximum allowable concentration for atmospheric contamination is 25 parts per million, as published in the A. M. A. Archives of Industrial Health ( 20 :266 [Sept.] 1959). This means that as little as 2.5 cc. of benzene, if evaporated, would provide the maximum allowable concentration level in 1,000 cu. ft. of space. One cubic centimeter of benzene entering the body through inhalation or skin absorption may be
Effect of the Time of Administration of Calcium Acetate on Phosphorus Binding
Authors: Lawrence R. Schiller, Carol A. Santa Ana, Mudassir S. Sheikh, Michael Emmett, John S. Fordtran
Journal: New England Journal of Medicine (1989)

Phosphorus binders are given to patients with renal failure to increase gastrointestinal excretion of phosphorus. To determine the relative importance of the binding of dietary as compared with endogenous phosphorus and to determine the optimal dose schedule, we gave either 4.4 g of calcium acetate (25 mmol of calcium) or a placebo to six normal subjects on each of seven different schedules in a randomized sequence. The net gastrointestinal balance of phosphorus and calcium was determined by a one-day lavage technique. After a meal containing approximately 12 mmol of phosphorus, the mean phosphorus absorption (±SE) measured 9.17±0.36 mmol (78 percent) with placebo but decreased to 3.81±0.58 mmol (31 percent) when calcium acetate was given immediately before the meal (representing binding of 5.36±0.77 mmol of phosphorus). Similar binding was observed when calcium acetate was given immediately after the meal and when half the dose was given before and half after the meal. In contrast, when calcium acetate was given two hours after the meal or while the subject was fasting, phosphorus binding was reduced to 2.00±0.52 mmol and 1.81±0.84 mmol, respectively. Calcium absorption from calcium acetate averaged 21±1 percent when the binder was given with a meal; absorption from calcium acetate averaged 40±4 percent when the binder was given while the subject was fasting. We conclude that calcium acetate increases fecal excretion of phosphorus by binding both dietary and endogenous phosphorus, but the binding of dietary phosphorus is quantitatively much more important. For the most efficient phosphorus binding, calcium (and presumably other phosphorus-binding cations) should be given with meals. (N Engl J Med 1989; 320:1110–3.)
Indomethacin-Induced Hyperkalemia in Three Patients With Gouty Arthritis
Authors: James W. Findling
Journal: JAMA (1980)

We describe three patients in whom severe, life-threatening hyperkalemia and renal insufficiency developed after treatment of acute gouty arthritis with indomethacin. This complication may result from an inhibition of prostaglandin synthesis and consequent hyporeninemic hypoaldosteronism. Careful attention to renal function and potassium balance in patients receiving indomethacin or other nonsteroidal anti-inflammatory agents, particularly in those patients with diabetes mellitus or preexisting renal disease, will help prevent this potentially serious complication. (<i>JAMA</i>244:1127-1128, 1980)
What Young Practitioners Want
Authors: P. McCormack
Journal: BMJ (1966)

Clinicians cannot have utter scientific con- firmation of much of their clinical beliefs.The relationship between heavy cigarettesmoking and lung cancer was a clinical impression long before it had been abundantly and incontrovertibly proved by statistics and other evidence, and the same kind of thing may happen in the case of Trasylol, showing that it has quite definitely beneficially influenced the course of acute pancreatitis.I shall therefore continue to use Trasylol in big doses in all cases of acute pancreatitis which come under my care.-I.iam, etc.,
LEFT ATRIAL APPENDAGE MORPHOLOGIC PATTERN DETERMINED BY COMPUTED TOMOGRAPHY IS A NOVEL PREDICTOR OF HIGH RISK PATIENT FOR EMBOLISM WITH ATRIAL FIBRILLATION
Authors: Nobuhiko Makino, Masami Nishino, Ayano Ishiyama, Akihiro Tanaka, Naotaka Okamoto, Naoki Mori, Yasuharu Lee, Takahiro Yoshimura, Daisuke Nakamura, Masayuki Taniike, Hiroyasu Kato, Yasuyuki Egami, Ryu Shutta, Hisaki Morita, Jun Tanouchi, Yoshio Yamada
Journal: Journal of the American College of Cardiology (2013)
Clinical Rubella with Arthritis Resulting from Reinfection
Authors: JEANETTE WILKINS
Journal: Annals of Internal Medicine (1972)

A 50-year-old woman with a history of clinical rubella and corroborating serologic evidence of this previous experience was inadventently exposed to Brown strain rubella virus in a controlled experimental situation. She developed classical signs of disease, including arthritis. This second episode of clinical rubella was confirmed by both virus isolation and significant increases in rubella antibodies. This is the first fully substantiated case in which rubella virus transmission to a "theoretically immune" person resulted in clinical rubella.
Nuclear proteins in the heart of the cardiomyopathic Syrian hamster. Phosphorylation of phenol-soluble nonhistone proteins.
Authors: C C Liew, M J Sole
Journal: Circulation Research (1978)

We examined incorporation of 32P into phenol-soluble nonhistone nuclear acidic proteins (NHNP) obtained from myolytic, hypertrophic, and failing phases of hamster cardiomyopathy. NHNP from these dystrophic hamster hearts were phosphorylated much less than their controls, despite a 9-fold increase in uptake of 32P into their nuclei. After fractionation of NHNP by isoelectrofocusing polyacrylamide gel electrophoresis, two major fractions focusing from pH 6.0 to 6.2 and 6.6 to 6.8 were highly phosphorylated in both the control and dystrophic hearts. The latter fraction was much more phosphorylated in the control. Two fractions of NHNP focusing at pH 4.9 and 5.1 were more highly phosphorylated in the dystrophic hearts than in the controls. Autoradiographs obtained from the two-dimensional polyacrylamide slab gel electrophoresis showed that two proteins (pH 4.9 and 5.1; mol wt 25,000 and 60,000, respectively) were highly phosphorylated in the dystrophic heart. There was no detectable phosphorylation of these proteins in the controls. These changes in the phosphorylation of cardiac NHNP may be important in determining the alteration of gene expression in hamster cardiomyopathy.
Family Practice in Hospitals
Authors: Barry D. Weiss
Journal: JAMA (1985)

FAMILY practice became medicine's 20th-recognized specialty in 1969, when both the American Medical Association's Council on Medical Education and the Advisory Board for Medical Specialties approved formation of the American Board of Family Practice.<sup>1-3</sup>In 1970 and again in 1976, the AMA's House of Delegates adopted a resolution stating that hospital departments of family practice should be established "with duties and responsibilities comparable to any other specialty department of the [hospital's] medical staff."<sup>4,5</sup>Coincident with the 1976 resolution, the Joint Commission on Accreditation of Hospitals (JCAH) authorized family physicians to exercise clinical privileges according to the rules and regulations of their own departments.<sup>6,7</sup> Despite recognition by these national organizations, family practice departments in hospitals have yet to be fully accepted. In many hospitals, departments of family practice are the only departments that do not have responsibility for recommending their own members for hospital privileges. Family physicians at
HTLV-III antibodies in US Army blood donors in West Germany
Authors: J. J. James
Journal: JAMA (1985)

To the Editor.—  The recent emphasis on the operating characteristics of the enzyme-linked immunosorbent assay (ELISA) human T-cell lymphotropic virus type III (HTLV-III) antibody test 1-3 and its role as a screening mechanism for the acquired immunodeficiency syndrome (AIDS) presents us with a crucial problem. We fail to see how the sensitivity and/or specificity of a screening test for an infectious disease can be precisely defined in the absence of either data on the true prevalence of infection within a population or a gold-standard confirmatory test to identify infection. To date, it seems that the operating characteristics of the HTLV-III ELISA antibody test have been defined (1) on the assumption that antibody seropositivity is a quantitative, predictive measure for viremia; (2) primarily among clinical populations; and (3) assuming, for the most part, the ELISA test itself as the most sensitive available. This is not to say that the HTLV-III antibody
Towards safer colonoscopy: a report on the complications of 5000 diagnostic or therapeutic colonoscopies.
Authors: F A Macrae, K G Tan, C B Williams
Journal: Gut (1983)

The diagnostic and therapeutic benefits of colonoscopy are well known but most large-scale surveys, especially those involving multiple centres, may underestimate the range and incidence of complications. The detailed records of 5000 colonoscopies in a specialist unit have been analysed and conclusions drawn which may help to make the procedure safer. The incidence of haemorrhage was 1% and bowel perforation 0.1%. All the major haemorrhages occurred during polypectomies over 2 cm in size. Secondary haemorrhage was an unpredictable occurrence, one to 14 days later. Three deaths followed colonoscopy: one cardiorespiratory death was related to oversedation; a second was due to mismanaged ischaemic colitis developing two days after traumatic instrumentation, and the third was due to peritonitis. Minor complications included thrombophlebitis, abdominal distension, and vasovagal episodes. Because of experience during the first half of the series and also due to improvements in instrumentation, the complication rate of the later part of the series was halved. Recommendations include the avoidance of oversedation, review of previous barium enema films so as to be aware of large polyps which are more likely to bleed, and the recognition of situations where perforation or septicaemia is likely to occur.
Circulating 1,5-Anhydroglucitol Levels in Adult Patients With Diabetes Reflect Longitudinal Changes of Glycemia
Authors: Janet B. McGill, Thomas G. Cole, William Nowatzke, Shannon Houghton, Erika B. Ammirati, Theresa Gautille, Mark J. Sarno
Journal: Diabetes Care (2004)

OBJECTIVE—1,5-Anhydroglucitol (1,5AG) is a major circulating polyol arising primarily from ingestion and excreted competitively with glucose. Japanese studies have demonstrated reduced concentrations of 1,5AG in serum in hyperglycemic patients in comparison with euglycemic subjects and a gradual normalization of 1,5AG values for patients responding to antihyperglycemic therapies. In this first U.S. study, we assessed the ability of 1,5AG measurements to monitor glycemic control in a cohort of 77 patients with diabetes (22 with type 1 diabetes, 55 with type 2 diabetes) who presented with suboptimal glycemic control at baseline (defined as HbA1c ≥7%). RESEARCH DESIGN AND METHODS—Each patient received therapies consisting of combinations of diabetes education, nutritional counseling, and addition or dose adjustment of various insulins or oral antihyperglycemic medications. Therapy was targeted to reduce mean HbA1c by ≥1.0% over the monitoring period. 1,5AG, HbA1c, fructosamine, and random glucose measurements were performed at baseline and at 2, 4, and 8 weeks after the initiation of therapy. RESULTS—1,5AG, fructosamine, and glucose values progressed significantly toward euglycemia by week 2 of monitoring (Wilcoxon’s signed-rank test, P &amp;lt; 0.05), with median changes of 93, −7, and −13% for 1,5AG, fructosamine, and glucose, respectively. In contrast, HbA1c values did not respond significantly to therapy until week 4. On an individual patient basis, 89.6% of patients displayed longitudinal changes of 1,5AG from baseline to week 8 in concordance with HbA1c. 1,5AG was also highly correlated with HbA1c and fructosamine (Spearman ρ = −0.6459 and −0.6751, respectively; both P &amp;lt; 0.0001). CONCLUSIONS—We conclude that 1,5AG responds sensitively and rapidly to changes in glycemia and monitors glycemic control in accordance with established markers.