tbuckley/cabot-search huggingface dataset:
Salivary Phosphate-Binding Chewing Gum Reduces Hyperphosphatemia in Dialysis Patients
Authors: Vincenzo Savica, Lorenzo A. Calo[Combining Grave Accent], Paolo Monardo, Paul A. Davis, Antonio Granata, Domenico Santoro, Rodolfo Savica, Rosa Musolino, Maria Cristina Comelli, Guido Bellinghieri
Journal: Journal of the American Society of Nephrology (2008)

In uremic patients, hyperphosphatemia is associated with cardiovascular calcification and increased cardiovascular mortality. Despite the use of phosphate binders, only half of hemodialysis (HD) patients achieve recommended serum phosphate levels. A hyperphosphoric salivary content, which correlates linearly with serum phosphate, has been reported in HD patients. We hypothesized that binding salivary phosphate during periods of fasting in addition to using phosphate binders with meals could improve the treatment of hyperphosphatemia. We assessed the phosphate-binding capacity of the natural polymer chitosan by (31)P nuclear magnetic resonance and established that 10 and 20% (wt/vol) middle viscosity chitosan solutions bind 30 and 50% of the phosphate contained in PBS, respectively. Thirteen HD patients with serum phosphate levels >6.0 mg/dl despite treatment with sevelamer hydrochloride chewed 20 mg of chitosan-loaded chewing gum twice daily for 2 wk at fast in addition to their prescribed phosphate-binding regimen. Salivary phosphate and serum phosphate significantly decreased during the first week of chewing; by the end of 2 wk, salivary phosphate decreased 55% from baseline (73.21 +/- 19.19 to 33.19 +/- 6.53; P < 0.00001), and serum phosphate decreased 31% from baseline (7.60 +/- 0.91 to 5.25 +/- 0.89 mg/dl; P < 0.00001). Salivary phosphate returned to baseline by day 15 after discontinuing the chewing gum, whereas serum phosphate levels took 30 d to return to baseline. Parathyroid hormone and serum calcium concentrations were not affected by the gum. In conclusion, adding salivary phosphate binding to traditional phosphate binders could be a useful approach for improving treatment of hyperphosphatemia in HD patients.
<i>S100A11</i>, A Putative Tumor Suppressor Gene, Is Overexpressed in Pancreatic Carcinogenesis
Authors: Kenoki Ohuchida, Kazuhiro Mizumoto, Seiji Ohhashi, Hiroshi Yamaguchi, Hiroyuki Konomi, Eishi Nagai, Koji Yamaguchi, Masazumi Tsuneyoshi, Masao Tanaka
Journal: Clinical Cancer Research (2006)

Abstract Purpose: Recent microarray analyses revealed that expression of S100A11 is up-regulated in pancreatic cancer. The aim of the present study was to evaluate the association of S100A11 with pancreatic carcinogenesis. Experimental Design: We measured S100A11 mRNA expression in various clinical samples related to pancreatic cancer and its precursor lesions, intraductal papillary mucinous neoplasm (IPMN) and pancreatic intraepithelial neoplasia, by quantitative reverse transcription-PCR. Results: Levels of S100A11 were significantly higher in pancreatic cancer (n = 22) and IPMN (n = 18) bulk tissues than in nonneoplastic bulk tissues (n = 22; P &amp;lt; 0.0001 for both). Levels of S100A11 did not differ between pancreatic cancer and IPMN bulk tissues. In microdissection analyses, however, IPMN cells (n = 21) expressed significantly higher levels of S100A11 than did cancer cells (n = 23; P = 0.003). The median level of S100A11 expression was higher in pancreatic intraepithelial neoplasia cells (n = 6) than in cancer cells. In pancreatic juice analyses, cancer-related (n = 24; P = 0.004) and IPMN-related (n = 18; P = 0.001) juice expressed significantly higher levels of S100A11 than did chronic pancreatitis–related juice (n = 23). Conclusions: The present data suggest that expression of S100A11, a putative tumor suppressor gene, is increased in the early stage of pancreatic carcinogenesis and decreased during subsequent progression to cancer. Analysis of the S100A11 level in pancreatic juice may be an effective tool for screening of patients with high-risk lesions that could progress to pancreatic cancer or detecting early-stage pancreatic cancer.
Conserved microRNA editing in mammalian evolution, development and disease
Authors: Maria Warnefors, Angélica Liechti, Jean Halbert, Delphine Valloton, Henrik Kaessmann
Journal: Genome biology (2014)

Mammalian microRNAs (miRNAs) are sometimes subject to adenosine-to-inosine RNA editing, which can lead to dramatic changes in miRNA target specificity or expression levels. However, although a few miRNAs are known to be edited at identical positions in human and mouse, the evolution of miRNA editing has not been investigated in detail. In this study, we identify conserved miRNA editing events in a range of mammalian and non-mammalian species.We demonstrate deep conservation of several site-specific miRNA editing events, including two that date back to the common ancestor of mammals and bony fishes some 450 million years ago. We also find evidence of a recent expansion of an edited miRNA family in placental mammals and show that editing of these miRNAs is associated with changes in target mRNA expression during primate development and aging. While global patterns of miRNA editing tend to be conserved across species, we observe substantial variation in editing frequencies depending on tissue, age and disease state: editing is more frequent in neural tissues compared to heart, kidney and testis; in older compared to younger individuals; and in samples from healthy tissues compared to tumors, which together suggests that miRNA editing might be associated with a reduced rate of cell proliferation.Our results show that site-specific miRNA editing is an evolutionarily conserved mechanism, which increases the functional diversity of mammalian miRNA transcriptomes. Furthermore, we find that although miRNA editing is rare compared to editing of long RNAs, miRNAs are greatly overrepresented among conserved editing targets.
The Risk of Recurrent Venous Thromboembolism in Men and Women
Authors: Paul A. Kyrle, Erich Minar, Christine Bialonczyk, Mirko Hirschl, Ansgar Weltermann, Sabine Eichinger
Journal: New England Journal of Medicine (2004)

Whether a patient's sex is associated with the risk of recurrent venous thromboembolism is unknown.We studied 826 patients for an average of 36 months after a first episode of spontaneous venous thromboembolism and the withdrawal of oral anticoagulants. We excluded pregnant patients and patients with a deficiency of antithrombin, protein C, or protein S; the lupus anticoagulant; cancer; or a requirement for potentially long-term antithrombotic treatment. The end point was objective evidence of a recurrence of symptomatic venous thromboembolism.Venous thromboembolism recurred in 74 of the 373 men, as compared with 28 of the 453 women (20 percent vs. 6 percent; relative risk of recurrence, 3.6; 95 percent confidence interval, 2.3 to 5.5; P<0.001). The risk remained unchanged after adjustment for age, the duration of anticoagulation, and the presence or absence of a first symptomatic pulmonary embolism, factor V Leiden, factor II G20210A, or an elevated level of factor VIII or IX. At five years, the likelihood of recurrence was 30.7 percent among men, as compared with 8.5 percent among women (P<0.001). The relative risk of recurrence was similar among women who had had their first thrombosis during oral-contraceptive use or hormone-replacement therapy and women in the same age group in whom the first event was idiopathic.The risk of recurrent venous thromboembolism is higher among men than women.
Cross-talk between Peroxisome Proliferator-Activated Receptor δ and Cytosolic Phospholipase A2α/Cyclooxygenase-2/Prostaglandin E2 Signaling Pathways in Human Hepatocellular Carcinoma Cells
Authors: Lihong Xu, Chang Han, Kyu Lim, Tong Wu
Journal: Cancer Research (2006)

Peroxisome proliferator-activated receptor delta (PPARdelta) is a nuclear transcription factor that is recently implicated in tumorigenesis besides lipid metabolism. This study describes the cross-talk between the PPARdelta and prostaglandin (PG) signaling pathways that coordinately regulate human hepatocellular carcinoma (HCC) cell growth. Activation of PPARdelta by its pharmacologic ligand, GW501516, enhanced the growth of three human HCC cell lines (HuH7, HepG2, and Hep3B), whereas inhibition of PPARdelta by small interfering RNA prevented growth. PPARdelta activation up-regulates the expression of cyclooxygenase (COX)-2, a rate-limiting enzyme for PG synthesis, and tumor growth. PPARdelta activation or PGE(2) treatment also induced the phosphorylation of cytosolic phospholipase A(2)alpha (cPLA(2)alpha), a key enzyme that releases arachidonic acid substrate for PG production via COX. Activation of cPLA(2)alpha by the calcium ionophore A23187 enhanced PPARdelta binding to PPARdelta response element (DRE) and increased PPARdelta reporter activity, which was blocked by the selective cPLA(2)alpha inhibitors. Consistent with this, addition of arachidonic acid to isolated nuclear extracts enhanced the binding of PPARdelta to DRE in vitro, suggesting a direct role of arachidonic acid for PPARdelta activation in the nucleus. Thus, PPARdelta induces COX-2 expression and the COX-2-derived PGE(2) further activates PPARdelta via cPLA(2)alpha. Such an interaction forms a novel feed-forward growth-promoting signaling that may play a role in hepatocarcinogenesis.
Alk3/Bmpr1a Receptor Is Required for Development of the Atrioventricular Canal Into Valves and Annulus Fibrosus
Authors: Vinciane Gaussin, Gregory E. Morley, Luk Cox, An Zwijsen, Kendra M. Vance, Lorin Emile, Yimin Tian, Jing Liu, Chull Hong, Dina Myers, Simon J. Conway, Christophe Depre, Yuji Mishina, Richard R. Behringer, Mark C. Hanks, Michael D. Schneider, Danny Huylebroeck, Glenn I. Fishman, John B.E. Burch, Stephen F. Vatner
Journal: Circulation Research (2005)

Endocardial cushions are precursors of mature atrioventricular (AV) valves. Their formation is induced by signaling molecules originating from the AV myocardium, including bone morphogenetic proteins (BMPs). Here, we hypothesized that BMP signaling plays an important role in the AV myocardium during the maturation of AV valves from the cushions. To test our hypothesis, we used a unique Cre/lox system to target the deletion of a floxed Alk3 allele, the type IA receptor for BMPs, to cardiac myocytes of the AV canal (AVC). Lineage analysis indicated that cardiac myocytes of the AVC contributed to the tricuspid mural and posterior leaflets, the mitral septal leaflet, and the atrial border of the annulus fibrosus. When Alk3 was deleted in these cells, defects were seen in the same leaflets, ie, the tricuspid mural leaflet and mitral septal leaflet were longer, the tricuspid posterior leaflet was displaced and adherent to the ventricular wall, and the annulus fibrosus was disrupted resulting in ventricular preexcitation. The defects seen in mice with AVC-targeted deletion of Alk3 provide strong support for a role of Alk3 in human congenital heart diseases, such as Ebstein’s anomaly. In conclusion, our mouse model demonstrated critical roles for Alk3 signaling in the AV myocardium during the development of AV valves and the annulus fibrosus.
Immunogenicity and tolerability of a multicomponent meningococcal serogroup B (4CMenB) vaccine in healthy adolescents in Chile: a phase 2b/3 randomised, observer-blind, placebo-controlled study
Authors: María Elena Santolaya, Miguel L O'Ryan, María Teresa Valenzuela, Valeria Prado, Rodrigo Vergara, Alma Muñoz, Daniela Toneatto, Gabriela Graña, Huajun Wang, Ralf Clemens, Peter M Dull
Journal: The Lancet (2012)
Case finding for patients at risk of readmission to hospital: development of algorithm to identify high risk patients
Authors: John Billings, Jennifer Dixon, Tod Mijanovich, David Wennberg
Journal: BMJ (2006)

<h3>Abstract</h3> <b>Objective</b> To develop a method of identifying patients at high risk of readmission to hospital in the next 12 months for practical use by primary care trusts and general practices in the NHS in England. <b>Data sources</b> Data from hospital episode statistics showing all admissions in NHS trusts in England over five years, 1999-2000 to 2003-4; data from the 2001 census for England. <b>Population</b> All residents in England admitted to hospital in the previous four years with a subset of "reference" conditions for which improved management may help to prevent future admissions. <b>Design</b> Multivariate statistical analysis of routinely collected data to develop an algorithm to predict patients at highest risk of readmission in the next 12 months. The algorithm was developed by using a 10% sample of hospital episode statistics data for all of England for the period indicated. The coefficients for 21 most powerful (and statistically significant) variables were then applied against a second 10% test sample to validate the findings of the algorithm from the first sample. <b>Results</b> The key factors predicting subsequent admission included age, sex, ethnicity, number of previous admissions, and clinical condition. The algorithm produces a risk score (from 0 to 100) for each patient admitted with a reference condition. At a risk score threshold of 50, the algorithm identified 54.3% of patients admitted with a reference condition who would have an admission in the next 12 months; 34.7% of patients were "flagged" incorrectly (they would not have a subsequent admission). At risk score threshold levels of 70 and 80, the rate of incorrectly "flagged" patients dropped to 22.6% and 15.7%, but the algorithm found a lower percentage of patients who would be readmitted. The algorithm is made freely available to primary care trusts via a website. <b>Conclusions</b> A method of predicting individual patients at highest risk of readmission to hospital in the next 12 months has been developed, which has a reasonable level of sensitivity and specificity. Using various assumptions a "business case" has been modelled to demonstrate to primary care trusts and practices the potential costs and impact of an intervention using the algorithm to reduce hospital admissions.
Differences in the sensorimotor response to distension between the proximal and distal stomach in humans
Authors: K-J Lee
Journal: Gut (2004)

It is not known which region of the stomach is responsible for symptom generation or whether symptoms induced by gastric distension are region specific. Also, it is unclear whether low level gastric distension has a modulatory role on gastric tone and mechanosensitivity.To define differences in the sensorimotor response to distension between proximal and distal gastric distension, and to determine the effects of low level gastric distension on gastric tone and mechanosensitivity.In 14 healthy volunteers, a double barostat assembly incorporating a distal (antral) and proximal (fundic) bag was introduced into the stomach. Pressure sensitivity tests with either bag were performed with and without simultaneous background distension of the other bag in a randomised manner. Proximal gastric accommodation to a meal was measured with and without simultaneous distal gastric distension.The distal stomach was less compliant than the proximal stomach to low level distension. Thresholds for first perception and discomfort, and symptom profiles did not differ between distal and proximal gastric distension. Simultaneously applied low level gastric distension of one segment did not affect gastric mechanosensitivity of the other segment. Both the proximal and distal stomach relax after ingestion of a meal. Simultaneous low level antral distension decreases proximal gastric accommodation to a meal.Compared with the proximal stomach, the distal stomach is less compliant but its mechanosensitivity is not different. Symptoms induced by gastric distension are not region specific and no spatial summation occurred. Meal induced relaxation occurs both in the proximal and distal stomach.
The role of cellular oxidative stress in regulating glycolysis energy metabolism in hepatoma cells
Authors: Dong-yun Shi, Fei-zhou Xie, Chao Zhai, Jeremy S Stern, Yang Liu, Shan-lin Liu
Journal: Molecular Cancer (2009)

The Warburg effect has been found in a wide spectrum of human cancers, however the underlying mechanisms are still unclear. This study aims to explore the role of cellular oxidative stress in relation to glycolysis and the Warburg effect in hepatoma cells. Various cell lines combining environmental hypoxia was used as an in vitro model to mimic tumor microenvironment in vivo. Superoxide dismutases (SOD) and xanthine oxidase (XO) gene transfection were used to produce various cellular redox levels. 2',7'-dichlorofluorescin (DCF) fluorescence and ESR spectrum were used to detect cellular reactive oxygen species (ROS). We found that endogenous or exogenous interference with the cellular oxidative stress can sensitively regulate glycolysis and the Warburg effect in hepatoma cells. Hepatoma cells displayed a high level of free radicals compared to immortalized normal hepatocyte cells. Increasing the level of ROS stress in hepatoma cells can directly upregulate HIF-1 and activate glycolysis without requirement of a hypoxic condition. This explains the mechanism whereby aerobic glycolysis, i.e. the Warburg effect arises. Either endogenously upregulating SOD or exogenously administration with antioxidant can, through downregulating ROS level, effectively regulate energy pathways in hepatoma cells and can inhibit the growth of tumor cells and xenograft tumors. This study suggests that the Warburg effect was related to an inherently high level of cellular ROS and HIF-1. Hepatoma cells adaptation to hypoxia for survival and rapid growth exploits oxidative stress ectopically activated glycolysis to compensate the energy supply. This specific mechanism in which tumor cells through cellular oxidative stress activate glycolysis to meet their energy metabolism requirement could be exploited to selectively kill tumor cells.
Survival in nephroblastoma treated according to the trial and study SIOP-9/GPOH with respect to relapse and morbidity
Authors: A. Weirich, R. Ludwig, N. Graf, U. Abel, I. Leuschner, G.M. Vujanic, O. Mehls, J. Boos, J. Beck, B. Royer-Pokora, P.A. Voûte
Journal: Annals of Oncology (2004)
The Tunnel at the End of the Light: My Endoscopic Journey in Six Decades by Peter Cotton: a book review
Authors: Peter Down
Journal: Gut (2012)

Written by Professor Peter B Cotton. Published privately by Peter Cotton, Charleston, South Carolina, USA, 2011, pp 261, no price given (softcover). ISBN-10 1452820465

Ask anyone attempting endoscopic retrograde cholangiopancreatography (ERCP) in the 1970s and you will be regaled with stories about Peter Cotton's master classes at the Middlesex Hospital. He had brought ERCP to Britain after spending 2 weeks with Kazuei Ogoshi in Japan in 1971. His skill was legendary and people flocked to his unit to watch him. As his reputation grew he travelled widely lecturing and demonstrating, and was called to treat royalty and celebrities all over the world. In 1986, to the dismay of many, he moved to the Duke University, North Carolina, and later to …
Genetic Counseling for Common Psychiatric Disorders: An Opportunity for Interdisciplinary Collaboration
Authors: Jehannine Austin, Angela Inglis, George Hadjipavlou
Journal: American Journal of Psychiatry (2014)

In their timely review of recent important genetic findings in psychiatric disordersspecifically, common and rare copy number variants (CNVs) in bipolar disorder, schizophrenia and autism spectrum disorders-Gershon and Alliey-Rodriguez (1) propose that these findings "must lead to profound changes" in genetic counseling and "propose that genetic counseling is more than risk prediction.
Suction drainage: a new approach to the treatment of empyema
Authors: B. Nigam
Journal: Thorax (1991)

Cardiac surgery in ThoraxFor some time Thorax has continued to accept papers concerned with cardiac surgery, though not cardiology, the reason being that there were few other outlets for the surgical papers.The number of journals available for papers on cardiac surgery has increased recently, so it was decided at the last editorial board meeting that Thorax should no longer accept papers concerned primarily with cardiac surgery.Thorax is very keen, however, to continue to publish papers on thoracic surgery and papers concerned with the effects of any form of surgery, including cardiac surgery, on the lungs.
Profound hypothermia with prolonged circulatory arrest. An experimental study.
Authors: J B Johnston, C Ushiro, K H Finley, F Gerbode
Journal: Thorax (1966)

The technique of biventricular bypass with the induction of profound hypothermia and circula- tory arrest has been practised widely as a means of performing open-heart surgery since it was introduced in 1959 (Drew and Anderson, 1959; Shields and Lewis, 1959; Gordon, Jones, Lud- dington, and Meyer, 1960).One of the limiting factors, using this technique in open-heart surgery, is that 50 to 60 minutes only of circulatory arrest will be tolerated at 100 C.This may mean that too little time is avail- able for completion of the intracardiac repair.This limitation has been overcome to some extent by recommencing the circulation for a short period, after which a further period of circulatory arrest is available.There is still a paucity of information as to how the body tolerates repeated periods of circulatory arrest.Another aspect of this method which is contro- versial is whether temporary or permanent neuro- logical damage may occur in patients subjected to profound hypothermia with or without circula- tory arrest.Thus Dubost, Blondeau, and Piwnica (1962) reported no neurological sequelae in a large experience.Drew (1961), who has used the method consistently since 1959, has noted only occasional post-operative neurological difficulties.Bjork and Hultquist (1960, 1962), and Egerton, Egerton, and Kay (1963), on the other hand, observed a high incidence of neurological com- plications, with frequent deaths from this cause, in a small series of patients operated upon with profound hypothermia with or without arrest of the circulation.The following studies were undertaken in an attempt to define some of the potentials and