tbuckley/cabot-search huggingface dataset:
c-Myc-mediated epigenetic silencing of MicroRNA-101 contributes to dysregulation of multiple pathways in hepatocellular carcinoma
Authors: Lei Wang, Xiang Zhang, Lin-Tao Jia, Si-Jun Hu, Jing Zhao, Jian-Dong Yang, Wei-Hong Wen, Zhe Wang, Tao Wang, Jun Zhao, Rui-An Wang, Yan-Ling Meng, Yong-Zhan Nie, Ke-Feng Dou, Si-Yi Chen, Li-Bo Yao, Dai-Ming Fan, Rui Zhang, An-Gang Yang
Journal: Hepatology (2013)

The MYC oncogene is overexpressed in hepatocellular carcinoma (HCC) and has been associated with widespread microRNA (miRNA) repression; however, the underlying mechanisms are largely unknown. Here, we report that the c-Myc oncogenic transcription factor physically interacts with enhancer of zeste homolog 2 (EZH2), a core enzymatic unit of polycomb repressive complex 2 (PRC2). Furthermore, miR-101, an important tumor-suppressive miRNA in human hepatocarcinomas, is epigenetically repressed by PRC2 complex in a c-Myc-mediated manner. miR-101, in turn, inhibits the expression of two subunits of PRC2 ( EZH2 and EED ), thus creating a double-negative feedback loop that regulates the process of hepatocarcinogenesis. Restoration of miR-101 expression suppresses multiple malignant phenotypes of HCC cells by coordinate repression of a cohort of oncogenes, including STMN1 , JUNB , and CXCR7 , and further increases expression of endogenous miR-101 by inhibition of PRC2 activation. In addition, co-overexpression of c-Myc and EZH2 in HCC samples was closely associated with lower expression of miR-101 ( P &lt; 0.0001) and poorer prognosis of HCC patients ( P &lt; 0.01). Conclusions : c-Myc collaborates with EZH2-containing PRC2 complex in silencing tumor-suppressive miRNAs during hepatocarcinogenesis and provides promising therapeutic candidates for human HCC. (Hepatology 2014;59:1850–1863)
Sympathetic stimulation and norepinephrine infusion modulate extracellular potassium concentration during acute myocardial ischemia.
Authors: M R Warner, T S Kroeker, D P Zipes
Journal: Circulation Research (1992)

The purpose of this study was to investigate whether sympathetic stimulation modulated the rise in extracellular K+ concentration ([K+]o) evoked by acute myocardial ischemia. In 35 alpha-chloralose-anesthetized dogs, we measured changes in [K+]o during acute myocardial ischemia in the presence and absence of sympathetic stimulation or norepinephrine infusion. A series of four 5-minute occlusions of the distal left anterior descending coronary artery (LAD) was completed in 18 dogs. Thirty minutes of reperfusion separated each LAD occlusion. Four to five K(+)-sensitive electrodes were inserted into the left ventricular midmyocardium that was perfused by the distal LAD. Lead II of the electrocardiogram, arterial pressure, and [K+]o were recorded, and the right atrium was paced at a constant cycle length. The first, second, and fourth LAD occlusions were done in the absence of sympathetic stimulation or norepinephrine infusion. The changes in [K+]o evoked by the first LAD occlusion differed (p &lt; 0.05) from those elicited by the second and fourth occlusions. However, the changes in [K+]o during the second and fourth LAD occlusions were similar (p &gt; 0.2) and served as controls for the responses obtained during the third occlusion. Two minutes before the third LAD occlusion, sympathetic stimulation (4 Hz) or norepinephrine infusion (0.25-0.5 micrograms/kg per minute i.v.) was begun and was continued until 2 minutes after reperfusion. We found that sympathetic stimulation and norepinephrine infusion increased (p &lt; 0.05) myocardial blood flow in both normal and ischemic tissue. The mean response recorded by 23 K(+)-sensitive electrodes in 11 dogs showed that sympathetic stimulation increased (p &lt; 0.001) the [K+]o at 1, 2, 3, 4, and 5 minutes after the onset of LAD occlusion compared with the second and fourth occlusions. In contrast, the mean response recorded by 20 K(+)-sensitive electrodes in seven dogs showed that norepinephrine infusion reduced (p &lt; 0.02) the [K+]o at 4 and 5 minutes after the onset of LAD occlusion. These data show that sympathetic stimulation increased the [K+]o evoked by acute myocardial ischemia, an effect that was not mimicked by the intravenous administration of norepinephrine.
P-loop mutations and novel therapeutic approaches for imatinib failures in chronic myeloid leukemia
Authors: Shundong Cang, Delong Liu
Journal: Journal of Hematology & Oncology (2008)

Imatinib was the first BCR-ABL-targeted agent approved for the treatment of patients with chronic myeloid leukemia (CML) and confers significant benefit for most patients; however, a substantial number of patients are either initially refractory or develop resistance. Point mutations within the ABL kinase domain of the BCR-ABL fusion protein are a major underlying cause of resistance. Of the known imatinib-resistant mutations, the most frequently occurring involve the ATP-binding loop (P-loop). In vitro evidence has suggested that these mutations are more oncogenic with respect to other mutations and wild type BCR-ABL. Dasatinib and nilotinib have been approved for second-line treatment of patients with CML who demonstrate resistance (or intolerance) to imatinib. Both agents have marked activity in patients resistant to imatinib; however, they have differential activity against certain mutations, including those of the P-loop. Data from clinical trials suggest that dasatinib may be more effective vs. nilotinib for treating patients harboring P-loop mutations. Other mutations that are differentially sensitive to the second-line tyrosine kinase inhibitors (TKIs) include F317L and F359I/V, which are more sensitive to nilotinib and dasatinib, respectively. P-loop status in patients with CML and the potency of TKIs against P-loop mutations are key determinants for prognosis and response to treatment. This communication reviews the clinical importance of P-loop mutations and the efficacy of the currently available TKIs against them.
Bayesian Coalescent Inference of Past Population Dynamics from Molecular Sequences
Authors: A. J. Drummond
Journal: Molecular Biology and Evolution (2005)

We introduce the Bayesian skyline plot, a new method for estimating past population dynamics through time from a sample of molecular sequences without dependence on a prespecified parametric model of demographic history. We describe a Markov chain Monte Carlo sampling procedure that efficiently samples a variant of the generalized skyline plot, given sequence data, and combines these plots to generate a posterior distribution of effective population size through time. We apply the Bayesian skyline plot to simulated data sets and show that it correctly reconstructs demographic history under canonical scenarios. Finally, we compare the Bayesian skyline plot model to previous coalescent approaches by analyzing two real data sets (hepatitis C virus in Egypt and mitochondrial DNA of Beringian bison) that have been previously investigated using alternative coalescent methods. In the bison analysis, we detect a severe but previously unrecognized bottleneck, estimated to have occurred 10,000 radiocarbon years ago, which coincides with both the earliest undisputed record of large numbers of humans in Alaska and the megafaunal extinctions in North America at the beginning of the Holocene.
Disease control rate (DRC) of bronchial asthma during pregnancy
Authors: Tatiana Luchnikova, Olga Prikhodko, Yuri Landyshev, Albina Babtseva, Elena Romantsova, Elena Smorodina
Journal: European Respiratory Journal (2013)

In recent years doctors from all around the world paying the high attention to the treatment of bronchial asthma in gestation during pregnancy. The main aim of this research is to get a better knowledge how the DCR of bronchial asthma in gestation during pregnancy influence the course of pregnancy, the fetus and the newborns. The research involves the explorations, descriptions of the bronchial asthmas clinical features, pregnancy and birth outcomes, newborns health (290 women who suffer from bronchial asthma were tested). The information was received through Asthma Control Test. Research results:  1 62.5% of the patients had have uncontrolled asthma;  2 37.5% of the patients had have controlled asthma;  The 1st group of the patients (51.7%) took control drugs (28% - cromones; 63,3% - inhalation corticosteroids; 8,7% – prednisolonum), the 2nd group of the patients (31%) because of the pregnancy took emergency drugs. The patients from the 1st group had had better respiratory function than the patients from the 2nd group (p  To sum up, the optimal asthma control during pregnancy will help in prevention of gestational complications and descendants’ health improvement.
Statins and the Risk of Colorectal Cancer: A Meta-Analysis of 18 Studies Involving More Than 1.5 Million Patients
Authors: Stefanos Bonovas, Kalitsa Filioussi, Christodoulos S. Flordellis, Nikolaos M. Sitaras
Journal: Journal of Clinical Oncology (2007)

Purpose Statins have been suggested to prevent colorectal cancer. Several epidemiologic studies have evaluated this association, whereas randomized controlled trials (RCTs) on cardiovascular outcomes provide relevant data as a secondary end point. Our aim was to examine the strength of this association through a detailed meta-analysis of the studies published on the subject in peer-reviewed literature. Methods A comprehensive search for studies published up to December 2006 was performed, reviews of each study were conducted, and data were abstracted. Before meta-analysis, the studies were evaluated for publication bias and heterogeneity. Pooled relative risk (RR) estimates with 95% CIs were calculated using the fixed- and random-effects models. Results Eighteen studies involving more than 1.5 million participants contributed to the analysis. They were grouped on the basis of study design, and separate meta-analyses were conducted. There was no evidence of an association between statin use and risk of colorectal cancer either among RCTs (RR = 0.95; 95% CI, 0.80 to 1.13; n = 6) or among cohort studies (RR = 0.96; 95% CI, 0.84 to 1.11; n = 3). However, statin use was associated with a modest reduction in the risk of colorectal cancer among case-control studies (RR = 0.91; 95% CI, 0.87 to 0.96; n = 9). Low evidence of publication bias or heterogeneity was found. Conclusion Our meta-analysis results do not support the hypothesis that statins strongly reduce the risk of colorectal cancer, when taken for management of hypercholesterolemia. However, we cannot rule out a modest reduction in risk or an effect associated with higher doses of statins.
UK legislation on analgesic packs: before and after study of long term effect on poisonings
Authors: Keith Hawton, Sue Simkin, Jonathan Deeks, Jayne Cooper, Amy Johnston, Keith Waters, Morag Arundel, William Bernal, Bridget Gunson, Mark Hudson, Deepak Suri, Kenneth Simpson
Journal: BMJ (2004)

<h3>Abstract</h3> <b>Objective</b> To evaluate the long term effect of legislation limiting the size of packs of analgesics sold over the counter. <b>Design</b> Before and after study. <b>Setting</b> Suicides in England and Wales, data from six liver units in England and Scotland and five general hospitals in England, and UK data on sales of analgesics, between September 1993 and September 2002. <b>Data sources</b> Office for National Statistics; six liver units in England and Scotland; monitoring systems in general hospitals in Oxford, Manchester, and Derby; and Intercontinental Medical Statistics Health UK. <b>Main outcome measures</b> Deaths by suicidal overdose with paracetamol, salicylates, or ibuprofen; numbers of patients admitted to liver units, listed for liver transplant, and undergoing transplantations for paracetamol induced hepatotoxicity; non-fatal self poisonings with analgesics and numbers of tablets taken; and sales figures for analgesics. <b>Results</b> Suicidal deaths from paracetamol and salicylates were reduced by 22% (95% confidence interval 11% to 32%) in the year after the change in legislation on 16 September 1998, and this reduction persisted in the next two years. Liver unit admissions and liver transplants for paracetamol induced hepatotoxicity were reduced by around 30% in the four years after the legislation. Numbers of paracetamol and salicylate tablets in non-fatal overdoses were reduced in the three years after the legislation. Large overdoses were reduced by 20% (9% to 29%) for paracetamol and by 39% (14% to 57%) for salicylates in the second and third years after the legislation. Ibuprofen overdoses increased after the legislation, but with little or no effect on deaths. <b>Conclusion</b> Legislation restricting pack sizes of analgesics in the United Kingdom has been beneficial. A further reduction in pack sizes could prevent more deaths.
A Paper on RECENT ADVANCES IN DIAGNOSTIC METHODS IN RENAL AFFECTIONS
Authors: R. O. Ward
Journal: BMJ (1931)

It was in I929 that a most important advance in the diagnosis of renal affections was made, and speedily be- came established as a method of examinationi of great yalue-namely, excretion urography; that is, the process of obtaining photographs of the urinary tract by means of substances which, when injected into the blood stream, are selectively excreted by the kidneys, and, inasmuch as they are opaque to X-rays, can be recorded on a photo- graphic film.The value of this method is at once obvious.It is useful, therefore, to consider briefly the technique employed, also the indications for its use, and some of the results that are obtained.Urology is to-day very fortunate in the accuracy of the various means available for diagnosis.The cystoscope, first developed into a serviceable instrument in I890, was the earliest and greatest advance.In I896 the first diagnosis of stone was made by X-rays.Radiology has made continuous progress since then, and there is no -reason to suppose that the limit of its usefulness is yet approached. INSTRUMENTAL PYELOGRAPHYA great advance occurred when pyelography was established in 1906 by Voelcker and Von Lichtenberg.This method, as is generally known, consists of the passage of a cystoscope, and by means of this, of a ureteric catheter up to the renal pelvis, and through this slender catheter is run into the pelvis and into the calyces leading from it, some radio-opaque substance.Collargol was one of the earliest of these, but to-day sodium iodide or bromide is employed, or one of the new contrast substances such, as uroselectan.Without entering into any detailed description it may be said that the pyelogram is then made by allowing the opaque fluid to enter in sufficient quantity to fill the kidney cavities.As soon as these
Interobserver Agreement in Describing the Ultrasound Appearance of Adnexal Masses and in Calculating the Risk of Malignancy Using Logistic Regression Models
Authors: Povilas Sladkevicius, Lil Valentin
Journal: Clinical Cancer Research (2014)

To estimate interobserver agreement with regard to describing adnexal masses using the International Ovarian Tumor Analysis (IOTA) terminology and the risk of malignancy calculated using IOTA logistic regression models LR1 and LR2, and to elucidate what explained the largest interobserver differences in calculated risk of malignancy.One hundred and seventeen women with adnexal masses were examined with transvaginal gray scale and power Doppler ultrasound by two independent experienced sonologists who described the masses using IOTA terminology. The risk of malignancy was calculated using LR1 and LR2. A predetermined risk of malignancy cutoff of 10% indicated malignancy.There were 94 benign, four borderline, and 19 invasively malignant tumors. There was substantial variability between the two sonologists in measurement results and some variability in assessment of categorical variables (agreement 40%-98%, Kappa 0.30-0.91). Interobserver agreement when classifying tumors as benign or malignant was 84% (98/117), Kappa 0.68 for LR1, and for LR2 85% (99/117), Kappa 0.68. When using LR1 and LR2, the interobserver difference in calculated risk was ≥ 25 percentage units in 9% (11/117) and 12% (14/117) of tumors, respectively. Differences in assessment of wall irregularity, acoustic shadowing, color score, and color flow in papillary projections explained most of these largest differences.Interobserver agreement in classifying tumors as benign or malignant using the risk of malignancy cutoff of 10% for LR1 and LR2 was good. However, because risk estimates may differ substantially between sonologists, one should be cautious with using the risk value for counseling patients about their individual risk.
Block of IKs, the slow component of the delayed rectifier K+ current, by the diuretic agent indapamide in guinea pig myocytes.
Authors: J Turgeon, P Daleau, P B Bennett, S S Wiggins, L Selby, D M Roden
Journal: Circulation Research (1994)

There is a high incidence of diuretic use among patients who develop exaggerated QT prolongation and polymorphic ventricular tachycardia (torsade de pointes) during treatment with action potential-prolonging agents. Diuretic-induced hypokalemia is thought to be the usual mechanism, but a direct effect of diuretic drugs on repolarizing currents is an additional possibility. Therefore, in this study, we examined the effects of the diuretic agents chlorthalidone and indapamide on the cardiac delayed rectifier current. In guinea pig ventricular myocytes, this current is made up of two components: IKr, a rapidly activating, inwardly rectifying current blocked by most action potential-prolonging antiarrhythmics, and IKs, a slowly activating component. In this preparation, indapamide blocked outward current in a time-, voltage- and concentration-dependent fashion, whereas chlorthalidone (1 mmol/L) was without effect. The following features of the effect of indapamide strongly suggest selective block of IKs: (1) Indapamide block was significantly greater with 5000-millisecond activating pulses (-43 +/- 5% at +50 mV [100 mumol/L indapamide]) than with 225-millisecond ones (-20 +/- 5%; n = 5, P &lt; .01), and the signature of the indapamide-sensitive current was a slowly activating delayed rectifier current. (2) The voltage dependence of indapamide block (EC50, 101 mumol/L at +50 mV and 196 mumol/L at +10 mV) was consistent with preferential block of IKs relative to IKr. (3) In the presence of indapamide, an envelope-of-tails test for IKr was satisfied. The drug-insensitive current had rectifying properties similar to those described for IKr in these cells.(ABSTRACT TRUNCATED AT 250 WORDS)
Massive Pulmonary Arteriovenous Fistula in the Newborn
Authors: ROBERT J. HALL, WILLIAM P. NELSON, HU A. BLAKE, JAMES P. GEIGER
Journal: Circulation (1965)

A case of massive pulmonary arteriovenous fistula, diagnosed and treated in the first week of life is reported. A concept of severely altered intrauterine and neonatal pulmonary blood flow is proposed, with consequent left ventricular overload manifested electrocardiographically by left axis deviation and left ventricular preponderance. Consideration of this malformation in seriously ill cyanotic infants with a radiographic density and these electrocardiographic changes is essential, since this is a surgically curable lesion.
Low–Saturated Fat Dietary Counseling Starting in Infancy Improves Insulin Sensitivity in 9-Year-Old Healthy Children
Authors: Tuuli Kaitosaari, Tapani Rönnemaa, Jorma Viikari, Olli Raitakari, Martti Arffman, Jukka Marniemi, Katariina Kallio, Katja Pahkala, Eero Jokinen, Olli Simell
Journal: Diabetes Care (2006)

OBJECTIVE—Insulin resistance is promoted already in childhood by obesity and possibly by high–saturated fat intake. We examined the effect of infancy onset biannually given dietary counseling on markers of insulin resistance in healthy 9-year-old children. RESEARCH DESIGN AND METHODS—Healthy 7-month-old infants (n = 1,062) were randomized to the intervention (n = 540) and control (n = 522) groups. Each year, two individualized counseling sessions were organized to each intervention family. The purpose of counseling was to minimize children’s exposure to known environmental atherosclerosis risk factors. Homeostasis model assessment of insulin resistance (HOMA-IR) index, serum lipids, blood pressure, and weight for height were determined in a random subgroup of 78 intervention children and 89 control children at the age of 9 years. RESULTS—Intervention children consumed less total and saturated fat than the control children (P = 0.002 and &amp;lt; 0.0001, respectively). The HOMA-IR index was lower in intervention children than in control children (P = 0.020). There was a significant association between saturated fat intake and HOMA-IR. In multivariate analyses including saturated fat intake, study group, and other determinants of HOMA-IR (serum triglyceride concentration, weight for height, and systolic blood pressure), study group was, whereas saturated fat intake was not, significantly associated with HOMA-IR. This suggests that the beneficial effect of intervention on insulin sensitivity was largely, but not fully, explained by the decrease in saturated fat intake. CONCLUSIONS—The long-term biannual dietary intervention decreases the intake of total and saturated fat and has a positive effect on insulin resistance index in 9-year-old children.
Phototherapeutic keratectomy for recurrent erosion syndrome in anterior basement membrane dystrophy11None of the authors has any financial interest in the entities described in this article.
Authors: Timothy B Cavanaugh, Diana M Lind, Paul E Cutarelli, Robert J.S Mack, Daniel S Durrie, Khathab M Hassanein, Charles E Graham
Journal: Ophthalmology (1999)
Effects of histamine and diamine oxidase activities on pregnancy: a critical review
Authors: L. Maintz, V. Schwarzer, T. Bieber, K. van der Ven, N. Novak
Journal: Human Reproduction Update (2008)

Histamine has been assumed to contribute to embryo–uterine interactions due to its vasoactive, differentiation and growth-promoting properties. However, its exact functions in pregnancy are unclear. The histamine-degrading enzyme diamine oxidase (DAO) is produced in high amounts by the placenta and has been supposed to act as a metabolic barrier to prevent excessive entry of bioactive histamine from the placenta into the maternal or fetal circulation. The literature available on PubMed published in English between 1910 and 2008 has been searched using the isolated and combined key words histamine, diamine oxidase, pregnancy, placenta, endometrium, miscarriage, implantation, pre-eclampsia, intrauterine growth retardation, diabetes and embryonic histamine-releasing factor (EHRF). High expression of the histamine-producing enzyme histidine decarboxylase in the placenta, histamine receptors at the feto–maternal interface and the existence of an EHRF suggest a physiological role of histamine during gestation. The balance between histamine and DAO seems to be crucial for an uncomplicated course of pregnancy. Reduced DAO activities have been found in multiple heterogeneous complications of pregnancy such as diabetes, threatened and missed abortion and trophoblastic disorders. Whether women with histamine intolerance suffer from more complicated pregnancies and higher abortion rates due to impaired DAO activities and if low DAO levels or genetic modifications in the DAO gene might therefore represent a prognostic factor for a higher risk of abortion, has not been investigated yet. Low activities of the histamine-degrading enzyme DAO might indicate high-risk pregnancies, although high intra- and interindividual variations limit its value as a screening tool.