tbuckley/cabot-search huggingface dataset:
Abstract 3899: A coactivator role of CARM1 for the dysregulated β-catenin activity in colorectal cancer cell growth and gene expression
Authors: Chen-Yin Ou, Philipp Manegold, Michael Kahn, Michael Stallcup
Journal: Cancer Research (2010)

Abstract Aberrant activation of Wnt/β-catenin signaling is recognized as a critical factor in the etiology of colorectal cancer. Evidence has suggested that dysregulated β-catenin activity is associated with the majority of colon cancers via activation of the expression of Wnt regulated oncogenes. In the nucleus, β-catenin regulates transcription by recruiting additional secondary coactivators. These secondary coactivators all have distinct and unique functions on Wnt/β-catenin target gene activation. For instance, CCAR1 (Cell Cycle and Apoptosis Regulator 1) has been shown to be important for the stable occupancy of β-catenin at the promoter of a Wnt target gene, and depletion of CCAR1 inhibits expression of several Wnt/β-catenin target genes and suppresses anchorage-independent growth of colon cancer cells (Ou CY et al. Journal of Biological Chemistry 2009;284(31);20629-20637). Here, we show that CARM1 (coactivator-associated-protein-arginine-methyltransferase 1) interacts with β-catenin and positively modulates β-catenin-mediated gene expression. In colorectal cancer cells, which have constitutively high Wnt/β-catenin activity, depletion of CARM1 inhibits the expression of Wnt/β-catenin-mediated oncogenes and suppresses anchorage-independent growth. In colorectal cancer cells that do not have constitutively high Wnt/β-catenin activity, we found that activation of Wnt/β-catenin signaling by treatment with Wnt3a increased the expression of a subset of Wnt target genes. Utilizing these cells, we demonstrated that CARM1 is specifically required for the expression of these Wnt3a-induced targets. Upon Wnt3a stimulation, CARM1-dependent dimethylation of histone H3 arginine (Arg) 17, at a Wnt-regulated promoter, is associated with the recruitment of both β-catenin and CARM1. Arg17 dimethylation by Wnt3a ligands is compromised by CARM1 knockdown, whereas Wnt3a-induced β-catenin recruitment is not affected. Finally, in a nude mouse xenograft model, compared with CARM1 knockdown cells, wild type HT29 tumor xenografts grow significantly faster. We conclude that CARM1 is an important modulator of Wnt/β-catenin transcription and may represent a novel target for therapeutic intervention in cancers involving aberrantly activated Wnt/β-catenin signaling. 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 3899.
Prevention of acute exacerbation of chronic hepatitis B infection in cancer patients receiving chemotherapy in a hepatitis B virus endemic area
Authors: Ping‐I Hsu, Kwok‐Hung Lai, Jin‐Shiung Cheng, Sung‐Shuo Kao, Yuan‐Rung Li, Wei‐Chih Sun, Wen‐Chi Chen, Kung‐Hung Lin, Chih‐An Shin, Po‐Hung Chiang, Yun‐Da Li, Wei‐Ting Ou, Hui‐Chun Chen, Hsien‐Chung Yu
Journal: Hepatology (2015)

Reactivation of hepatitis B viral (HBV) infection in cancer patients undergoing chemotherapy may cause interruption of chemotherapy and lead to liver failure and death. In our institute, a computerized order entry–based alert system was introduced in September 2011 to remind healthcare providers of HBV testing when prescribing chemotherapy. Since August 2012, an order entry–based therapeutic control system has been applied to ensure HBV prophylaxis during chemotherapy. This retrospective cohort study included cancer patients receiving chemotherapy in the Kaohsiung Veterans General Hospital from November 2009 to June 2013. The prechemotherapy HBV screening rate, HBV prophylactic rate, and severe HBV acute exacerbation rate were compared between stages with different order systems. Newly diagnosed cancer patients (n = 2512) were included. The HBV testing rate in the screening reminder stage was higher than that in the educational stage (93.5% versus 40.2%, P &lt; 0.001), whereas the adequate HBV prophylactic rates in the two order entry–based stages were comparable (41.1% versus 39.2%). Patients in the order entry–based therapeutic control stage had a higher HBV screening rate (99.3% versus 40.2%, P &lt; 0.001) and a higher HBV prophylactic rate (95.8% versus 39.2%, P &lt; 0.001) than those in the educational stage. Additionally, the severe HBV acute exacerbation rate in the therapeutic control stage was lower than those in the educational and screening reminder stages (0% versus 1.2% and 1.2%, respectively; both P &lt; 0.01). Conclusion : A computerized order entry–based therapeutic control system can provide excellent prechemotherapy HBV screening for cancer patients undergoing chemotherapy and can effectively prevent severe acute exacerbation of HBV infection in hospitals among HBV endemic areas. (H epatology 2015;62:387–396
Colonisation and infection due to Enterobacteriaceae producing plasmid-mediated AmpC β-lactamases
Authors: Jesús Rodríguez-Baño, Elisenda Miró, Macarena Villar, Alicia Coelho, Mónica Gozalo, Nuria Borrell, Germán Bou, M. Carmen Conejo, Virginia Pomar, Belén Aracil, Nieves Larrosa, Jesús Agüero, Antonio Oliver, Ana Fernández, Jesús Oteo, Alvaro Pascual, Ferran Navarro
Journal: Journal of Infection (2011)
Homing-in on the origin of biliary steroids
Authors: MARTIN C CAREY
Journal: Gut (1997)

See article on page 700 

The raison d’etre of bile is to provide a conduit to eliminate excess cholesterol from the organism.1 Biliary secretion accomplishes this function in two ways. The liver secretes unesterified (free) cholesterol molecules into bile and also converts cholesterol molecules into bile acids, which are secreted as water soluble anions (bile salts). Bile salt synthesis from cholesterol compensates for obligatory faecal loss (as acidic sterols) during enterohepatic cycling, and this feedback control is regulated by the efficiency of bile salt return from the intestine. In a healthy human of ideal body weight, de novo synthesis amounts to about 250 mg a day and the bile salt pool, which approximates 3 g, cycles 8 to 12 times a day; therefore, the contribution of bile salt synthesis to biliary secretion is approximately 1%. In contrast to the efficiency of the enterohepatic circulation, 50% of the 1000 mg of cholesterol secreted daily into bile is lost in faeces as bacterial metabolic products (neutral sterols) in faeces, thereby exceeding the loss of cholesterol as acidic sterols by a factor of 2 to 1.

Knowledge of the precursor sources and disposition of biliary cholesterol and bile salts is important for its own sake and to provide targets for new drugs because of the high prevalence rates of atherosclerosis and cholesterol gallstones in Western societies. In both animals and humans, the contributions of de novo cholesterol synthesis to biliary cholesterol secretion, as well as bile salt synthesis, are now considered to be of minor quantitative importance, with estimates as low as 10%.2 Clearly, the evidence suggests that biliary cholesterol and bile salt molecules derive principally from preformed cholesterol in plasma lipoproteins.2-4 Now, Hillebrant and colleagues (see page 700) have narrowed the focus and …
The Solihull Stretcher
Authors: H. B. Watson, P. H. Dennison
Journal: BMJ (1965)

to necrosis with granulocyte infiltration-were found.The lungs showed chronic venous con- gestion in addition to the acute congestion.There were stones in the gall-bladder and micro- scopy showed chronic cholangitis.In view of the changes these oral contra- ceptives may cause in the blood coagulation mechanism,1 and in particular in view of the study in which similar drugs were found to cause thrombi in the hearts of hamsters,' these findings tempt one to postulate that this case may be an example of thrombosis of similar aetiology.The dosage in this case was low, but she was obviously intolerant, as she developed side-effects.Could it be that detoxication of the drugs had been hindered by her liver disease ?It now appears to be accepted that venous thrombosis with subsequent embolic compli- cations may be expected in women on these drugs' (in, as Tyler' puts it, a state of pseudo- pregnancy), but that the danger is probably no greater than that in pregnancy.However, the present case, and possibly Zilkha's' cases also, indicate that the possibility of arterial thrombosis may also exist.No conclusions can be drawn from single cases, but it is suggested that we should continue to be on the look-out for similar cases, and above all be aware of the possible dangers of oral contraception.-Iam, etc.,
Injury in Sport: The Physiology, Prevention and Treatment of Injuries Associated With Sport
Authors: Allan J. Ryan
Journal: JAMA (1965)

<h3>The ABC's of Athletic Injuries and Conditioning.</h3> By Albert Barnett Ferguson, Jr. and Jay Bender. 253 pp, with illus. $9.25. Williams &amp; Wilkins Co., 428 E Preston St, Baltimore 2, 1964 <h3>Injuries.</h3> Edited by George J. Curry. 256 pp, with illus. $6.50. G. P. Putnam's Sons, 200 Madison Ave, New York, 1964 Physician-interest in the prevention and management of athletic injuries has become increasingly important with the tremendous growth in participation in sports.<i>Injury in Sport</i>is more than simply a study of this particular problem. It is actually a comprehensive text in the field of sports medicine, which is already a recognized specialty in Europe and will soon become one here. The book is divided into three parts. The first deals with human anatomy and physiology as they relate to movement, exercise, fitness, and training. The individual articles are excellently conceived from the standpoint of content and clarity of
Copper Containers Not Sufficiently Germicidal to Typhoid Bacilli in Water.
Authors: J. A. Egan
Journal: JAMA (1904)

Springfield,Ill., Oct. 5, 1904. <h3>To the Editor:</h3> —According to newspaper reports of the latter part of August Dr. Edward Martin, director of public health and charities, Philadelphia, stood sponsor for the following statement: "Typhoid fever germs may be removed from water without boiling or filtering. It is only necessary to let water stand for four hours in a copper kettle in a living-room temperature or twenty-four hours in a refrigerator. The water will receive sufficient colloidal impregnation from the vessel to kill typhoid fever and cholera germs." At about the same time the newspapers published an announcement that municipalities and communities suffering from or threatened with the presence of typhoid germs in drinking water were requested to call on the Secretary of Agriculture to render assistance; that the Department of Agriculture, after exhaustive investigations, had found a remedy for the destruction of typhoid bacilli in the simple retention of
Occlusive Renal Artery Disease and Hypertension
Authors: E. F. Poutasse
Journal: JAMA (1962)

<h3>To the Editor:—</h3> Regarding my recent article, "Diagnosis and Treatment of Occlusive Renal Artery Disease and Hypertension," which was published inThe Journalon Dec. 16, 1961 (<b>178</b>:1078), several points deserve further comment. A recent review of our cases of hypertension by Dr. L. Wilson and Dr. Harriet P. Dustan has shown that a familial tendency for hypertensive disease was about as common in patients with renal hypertension as it was in patients with essential hypertension. The systolic bruit characteristic of occlusive renal artery disease was not heard in half of our series of patients, as stated in the text; but now with greater attention to its detection, this sign is being found in a significant number of patients. Recently, I have been using autogenous vein grafts to replace the renal artery following excision of a long, diseased segment. The strength of the sodium nitroprusside solution used for vasodepression
Marfan Syndrome, Hypertrophic Cardiomyopathy Findings Underline Avoidance of Some Sports
Authors: Marsha F. Goldsmith
Journal: JAMA (1992)

BASKETBALL RATES a lot of attention from many Americans now and for the next few months. But there are some young people who had better limit their interest to watching the sport and not even think about playing it lest they literally risk sudden death.  Physicians have long known that participation in strenuous sports is not a great idea for people with one of at least two different cardiac abnormalities. But until their genetic markers were recently discovered, young men and women with either the Marfan syndrome or familial hypertrophic cardiomyopathy often followed athletic pursuits without any idea that their genes made it  The problem is idespread enough that molecular biologists are pleased to have a new way to divert individuals with the telltale genes away from competitive sports and toward other, less life-threatening, endeavors. At the 65th Scientific Sessions of the American Heart Association, held in New Orleans, La,
Malpractice Insurance and Medical Defense.
Authors: E. H. Merritt
Journal: JAMA (1905)

Fort Wayne, Ind., April 11, 1905. <h3>To the Editor:</h3> —InThe Journal, April 1, 1905, is an editorial commenting on the recent opinion of Attorney-General Mullan of Iowa in which he held that "physicians can not take out insurance in that state against malpractice suits." You state that "considering the fact that probably nine-tenths of all malpractice suits are pure blackmail, instigated by quacks and foraging lawyers, the finding seems to be a peculiar one." The opinion does not seem to us a peculiar one. It is the only rational opinion which could have been rendered, and but confirms the opinions of attorneys general of a number of other states. The "physicians' liability policies" issued by casualty insurance companies purport to defend any malpractice suit brought against the policy holder, and in the event of a judgment being rendered against the physician, to pay the same within the limits provided
Intermittent Trimethoprim-Sulfamethoxazole Compared with Dapsone-Pyrimethamine for the Simultaneous Primary Prophylaxis of Pneumocystis Pneumonia and Toxoplasmosis in Patients Infected with HIV
Authors: Daniel Podzamczer
Journal: Annals of Internal Medicine (1995)

Objective: To evaluate the efficacy and safety of two oral, intermittent drug regimens for the simultaneous primary prophylaxis of Pneumocystis carinii pneumonia and toxoplasmosis in patients with HIV infection. Design: Nonblinded randomized study: Patients received either 1) trimethoprim-sulfamethoxazole [160 mg-800 mg orally twice a day on a thrice weekly regimen] or 2) 100 mg of dapsone plus 50 mg of pyrimethamine orally twice weekly. Setting: University teaching hospital in Barcelona. Patients: 230 patients infected with HIV who had CD4 cell counts of less than 200 × 106/L and who had not previously had P. carinii pneumonia or toxoplasmosis. Measurements: Clinical and biological evaluations; adverse reactions; and end points of P. carinii pneumonia, toxoplasmosis, and death. Results: After a median follow-up of 430 days, 6 (6.3%) of 96 evaluable patients receiving dapsone-pyrimethamine and 0 of 104 evaluable patients receiving trimethoprim-sulfamethoxazole developed P. carinii pneumonia (P < 0.0001). The cumulative rates of P. carinii pneumonia at 12 and 24 months were 0% and 0% for patients receiving trimethoprim-sulfamethoxazole and 4% and 11% for patients receiving dapsone-pyrimethamine (Mantel-Cox, P = 0.014). However, only one episode of P. carinii pneumonia developed while patients were taking these drugs. No differences were observed for toxoplasmosis (one episode in the trimethoprim-sulfamethoxazole arm and two in the dapsone-pyrimethamine arm), with cumulative rates at 12 and 24 months of 0% and 4% for the trimethoprim-sulfamethoxazole arm and 2% and 7% for the dapsone-pyrimethamine arm (P = 0.65). Similar mortality rates were observed during follow-up (P = 0.85). Nineteen patients (9.5%) discontinued therapy with the drugs because of adverse effects: Ten were in the trimethoprim-sulfamethoxazole arm and 9 were in the dapsone-pyrimethamine arm (P = 0.95). Conclusions: Thrice-weekly trimethoprim-sulfamethoxazole is an effective and well-tolerated regimen for the simultaneous primary prophylaxis of P. carinii pneumonia and toxoplasmosis in patients infected with HIV. Twice-weekly dapsone-pyrimethamine appears to be a safe and effective alternative.
Foxa1 and Foxa2 regulate bile duct development in mice
Authors: Zhaoyu Li, Peter White, Geetu Tuteja, Nir Rubins, Sara Sackett, Klaus H. Kaestner
Journal: Journal of Clinical Investigation (2009)

The forkhead box proteins A1 and A2 (Foxa1 and Foxa2) are transcription factors with critical roles in establishing the developmental competence of the foregut endoderm and in initiating liver specification. Using conditional gene ablation during a later phase of liver development, we show here that deletion of both Foxa1 and Foxa2 (Foxa1/2) in the embryonic liver caused hyperplasia of the biliary tree. Abnormal bile duct formation in Foxa1/2-deficient liver was due, at least in part, to activation of IL-6 expression, a proliferative signal for cholangiocytes. The glucocorticoid receptor is a negative regulator of IL-6 transcription; in the absence of Foxa1/2, the glucocorticoid receptor failed to bind to the IL-6 promoter, causing enhanced IL-6 expression. Thus, after liver specification, Foxa1/2 are required for normal bile duct development through prevention of excess cholangiocyte proliferation. Our data suggest that Foxa1/2 function as terminators of bile duct expansion in the adult liver through inhibition of IL-6 expression.
Gamma Hydroxy Butyrate (GHB)
Authors: Rosemary B. Lane
Journal: JAMA (1991)

<h3>To the Editor. —</h3> The January 23/30, 1991, issue of<i>JAMA</i>included a report from the Centers for Disease Control (CDC) (<i>MMWR</i>. 1990;39:861-863) on illicit use of gamma hydroxy butyrate (GHB).<sup>1</sup>This was of great interest to me because, from 1968 to 1976,I worked as a pediatrician in a church hospital in rural Africa (Hôpital Enongal in Ebolowa, Cameroon). When GHB became available from France as an anesthetic agent, we began using this product extensively. We rapidly stopped using it in adults because it did not produce a satisfactory level of anesthesia. However, in children it turned out to be very valuable. I personally supervised over 100 pediatric anesthesias, using GHB as the sole anesthetic agent in most cases. Very rarely, we used supplementation with ethyl ether for muscle relaxation in closing large abdominal wounds. This was done under relatively primitive surroundings without supplemental oxygen or a conventional anesthesia
The Relationship of Molecular Markers of <i>p53</i> Function and Angiogenesis to Prognosis of Stage I Epithelial Ovarian Cancer
Authors: Michael J. Goodheart, Justine M. Ritchie, Stephen L. Rose, John P. Fruehauf, Barry R. De Young, Richard E. Buller
Journal: Clinical Cancer Research (2005)

Abstract Purpose: Multiple angiogenic factors may influence tumor progression and metastasis. Several are modified by the p53 gene. We sought to identify molecular markers for high-risk stage I epithelial ovarian cancers. Experimental Design: Seventy-seven consecutive stage I epithelial ovarian cancers were evaluated for p53, CD31 microvessel density, thrombospondin-1, vascular endothelial growth factor (VEGF), p21 immunohistochemical staining, and p53 gene mutations. Molecular marker impact upon disease-specific survival, disease recurrence, and distant recurrence was evaluated with Cox regression. Results: There were 12 deaths from disease. Twelve of the 77 tumors contained p53 mutations—10 missense and 3 null (one tumor had two mutations). Fesddration Internationale des Gynaecologistes et Obstetristes substage (IA/IB versus IC; P &amp;lt; 0.001) and VEGF staining (P = 0.02) were significant in bivariate models with relationship to disease-specific survival. Stage (P = 0.0004), grade (P = 0.008), histology (P = 0.0025), p53 dysfunction (positive stain and/or mutation; P = 0.048), and microvessel density (P = 0.04) were significant in bivariate models with relationship to time to recurrence. In multivariate analyses among stage IC patients, failure to receive chemotherapy and microvessel density were associated with disease-specific survival, time to recurrence, and time to distant recurrence with hazard ratios of 4.8 to 44.1. Conclusions: The p53-dependent molecular markers of angiogenesis are of limited utility in developing a clinical strategy for postoperative management of stage I ovarian carcinoma. Microvessel density impacts survival and metastasis for high-risk stage IC disease. Adjuvant chemotherapy is necessary, but not sufficient, for cure of high-risk stage I epithelial ovarian cancers.
Standard Orthotopic Heart Transplantation Versus Total Orthotopic Heart Transplantation
Authors: Geneviève Derumeaux, Gilbert Habib, Dominique Mouton Schleifer, Pierre Ambrosi, Jean Paul Bessou, Dominique Metras, Alain Cribier, Roger Luccioni, Robert Soyer, Brice Letac
Journal: Circulation (1995)

Background After standard orthotopic heart transplantation (Sd HT), the enlarged resultant atria may promote atrial thrombosis. The purpose of this study was to compare the incidence of spontaneous echo contrast and left atrial thrombosis after Sd HT and total orthotopic (Tot HT) heart transplantation. Methods and Results Transesophageal echocardiography (TEE) was performed in 75 patients with Sd HT and in 20 patients with Tot HT. Despite the use of antiplatelet therapy, an acute arterial embolism occurred in 11 (15%) of the 75 patients with Sd HT but in none of the 20 Tot HT patients. All patients were in sinus rhythm. Left ventricular ejection fraction was similar in Sd HT and Tot HT patients. Left atrial diameter was smaller in Tot HT patients than in Sd HT patients (41±4 versus 58±6 mm, P &lt;.001). In Sd HT patients, spontaneous echo contrast was present in 43 patients (57%) and was associated with left atrial thrombus in 20 patients (on the left atrial appendage in 12 patients, on the posterior wall in 6, and on the suture in 2). No thrombus was detected by transthoracic echocardiography; all thrombi were detected by TEE. On the other hand, no left atrial thrombus was observed in Tot HT patients, and only 1 patient had spontaneous echo contrast. Of the 11 Sd HT patients who experienced an arterial embolism, 5 had both spontaneous echo contrast and left atrial thrombus and 5 had only spontaneous echo contrast. Conclusions This study demonstrates a high rate of left atrial thrombus after Sd HT and emphasizes the role of TEE in the follow-up of these patients. The therapeutic implications are the need for a preventive anticoagulant therapy in the high-risk population receiving Sd HT diagnosed with TEE and the consideration of Tot HT as a better surgical approach as far as thrombotic complications are concerned.
The Portsmouth Casualty Survey
Authors: C. P. B. Parry, B. D. Cooper, M. E. Shelswell, G. E. Dunkerley, R. A. Denham, C. M. M. Murray
Journal: BMJ (1962)

As the reception, treatment, and disposal of casualties are becoming such an urgent problem it was decided in 1960 to analyse every new case attending the casualty department at the Royal Portsmouth Hospital for a period of six months.In this paper the results of that review are given.
Germline RAD51C mutations confer susceptibility to ovarian cancer
Authors: Chey Loveday, Clare Turnbull, Elise Ruark, Rosa Maria Munoz Xicola, Emma Ramsay, Deborah Hughes, Margaret Warren-Perry, Katie Snape, Diana Eccles, D Gareth Evans, Martin Gore, Anthony Renwick, Sheila Seal, Antonis C Antoniou, Nazneen Rahman
Journal: Nature Genetics (2012)