tbuckley/cabot-search huggingface dataset:
Abstract 1230: Wnt5a-dependent induction of senescence suppresses epithelial ovarian cancer
Authors: Benjamin G. Bitler, Jasmine P. Nicodemus, Hua Li, Qi Cai, Keri Soring, Michael J. Birrer, Denise C. Connolly, Andrew K. Godwin, Paul Cairns, Hong Wu, Rugang Zhang
Journal: Cancer Research (2011)

Abstract Epithelial Ovarian Cancer (EOC) remains the most lethal gynecological malignancy in US and is the fifth leading cause of cancer deaths among American women. Thus, there is an urgent need to understand the etiology of EOC to develop novel therapies for this disease. Wnt5a is classified as a non-canonical Wnt ligand. Here, we demonstrated that Wnt5a is expressed at significantly lower levels in human EOC cell lines and in primary human EOC compared with either normal ovarian surface epithelial cells (p=0.039) or fallopian tube epithelial cells (p&amp;lt;0.001). Importantly, expression of Wnt5a in primary human EOC inversely correlates with tumor stage (p=0.003) but not tumor grade (p=0.086). Interestingly, Wnt5a expression is significantly lower in Type II high-grade serous EOC compared to Type I EOC that includes low-grade serous, mucinous, clear cell and endometrioid subtypes of EOC (p=0.005). In addition, we discovered that hypermethylation of promoter CpG island contributes to Wnt5a downregulation in human EOC cells. Significantly, restoration of Wnt5a expression in human EOC cells promoted senescence of EOC cells and resulted in a dramatic decrease in cell proliferation both in vitro and in vivo in an orthotopic model of EOC in the ovary of SCID mice. Mechanistically, Wnt5a inhibited canonical Wnt/beta-catenin signaling and resulted in the activation of senescence-promoting histone repressor A/PML pathway. In summary, we show that Wnt5a is often expressed at lower levels in primary human EOC and Wnt5a expression suppresses the growth of EOC cells by triggering senescence through antagonizing canonical Wnt signaling. Our data imply that the cell of origin between Type I and Type II EOC is different. These results also suggest that loss of Wnt5a expression is a putative marker of EOC and that non-canonical Wnt signaling is a potent target for developing novel EOC therapeutics. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 1230. doi:10.1158/1538-7445.AM2011-1230
Food and drugs alter response to anaesthesia
Authors: J. H. Tanne
Journal: BMJ (1998)

Common foods and widely used prescription and over the counter drugs may alter patients' response to muscle relaxants and anaesthetic agents, according to studies presented at the American Aszsociation of Anesthesiologists' meeting in Orlando, Florida.

Potatoes, tomatoes, and aubergines contain natural insecticide compounds called solanaceous glycoalkaloids that even in small amounts may greatly slow the metabolism of muscle relaxants and anaesthetic agents such as suxamethonium, mivacurium, and cocaine, said Daniel McGehee of the department of anaesthesia …
Competing interests concerns must not stop GPs from commissioning primary care, NHS chief says
Authors: A. Ferriman
Journal: BMJ (2014)

Clinical commissioning groups (CCGs) in England will get new powers under an initiative announced this week by Simon Stevens, the new chief executive of NHS England.

He told the annual conference of NHS Clinical Commissioners, the membership organisation of CCGs, that he would be writing to CCGs next week with details of how they could submit expressions of interest in taking on enhanced powers to jointly commission primary care services with NHS England.

CCGs would need to show how they would ensure transparent and fair governance, while NHS England would continue to have an oversight role …
Balloon blocks backflow of blood, relieves testicular varicoceles
Authors: Phil Gunby
Journal: JAMA (1981)

Scrotal discomfort brings an estimated 12,000 American men to surgeons annually for internal spermatic vein ligation to relieve testicular varicoceles. Now Baltimore physicians say they can obtain the same result by occluding the vein with detachable silicone balloons. This work is being done at The Johns Hopkins University Medical Institutions, where the procedure is being performed two or three times per week on an outpatient basis. In addition, the Baltimore investigators are studying a possible association between varicoceles and male subfertility to determine what potential the procedure may have for alleviating this problem. (The latter application is the brainchild of Patrick C. Walsh, MD, professor and chairman of the Department of Urology.) Robert I. White, Jr, MD, professor of radiology, explained the procedure this way at the Radiological Society of North America (RSNA) meeting in Dallas: After a local anesthetic is administered to the groin area, a catheter is
Pathology related to chronic arsenic exposure.
Authors: Jose A Centeno, Florabel G Mullick, Leonor Martinez, Norbert P Page, Herman Gibb, David Longfellow, Claudia Thompson, Elena R Ladich
Journal: Environmental Health Perspectives (2002)

Millions now suffer the effects of chronic arseniasis related to environmental arsenic exposure. The biological mechanisms responsible for arsenic-induced toxicity and especially chronic effects, including cancer, are not well known. The U.S. Armed Forces Institute of Pathology (AFIP) is participating in an international research effort to improve this understanding by the development of the International Tissue and Tumor Repository for Chronic Arsenosis (ITTRCA). The ITTRCA obtains, archives, and makes available for research purposes, tissues from subjects exposed to arsenic. We provide here a short overview of arsenic-induced pathology, briefly describe arsenic-induced lesions in the skin and liver, and present five case reports from the ITTRCA. Arsenic-induced skin pathology includes hyperkeratosis, pigmentation changes, Bowen disease, squamous cell carcinoma, and basal cell carcinomas. A unique spectrum of skin lesions, known as arsenical keratosis, is rather characteristic of chronic arseniasis. Bowen disease, or squamous cell carcinoma in situ of the skin, has been well documented as a consequence of arsenical exposure. A spectrum of liver lesions has also been attributed to chronic arseniasis. Of these, hepatocellular carcinoma, angiosarcoma, cirrhosis, and hepatoportal sclerosis have been associated with arsenic exposure. We present case reports that relate to these health conditions, namely, squamous cell carcinoma, basal cell carcinoma, and Bowen disease of the skin and hepatocellular carcinoma and angiosarcoma of the liver. Four patients had been treated with arsenical medications for such conditions as asthma, psoriasis, and syphilis, and one case occurred in a boy chronically exposed to arsenic in drinking water.
PWE-222 Audit of upper GI cancer diagnosis by endoscopy: are diagnoses being missed?
Authors: V M Patel, J I Wyatt, S M Everett
Journal: Gut (2012)

<h3>Introduction</h3> Gastric and oesophageal cancers have a high mortality rate, particularly if diagnosed at a late stage. We aimed to determine whether Upper Gastrointestinal (UGI) cancers are being missed either endoscopically or histologically in Leeds, and the reasons for any delays identified. <h3>Methods</h3> As part of our rolling annual audit programme, histopathology records were gathered for all UGI cancers detected between September 2009 and August 2010 at Leeds Teaching Hospitals Trust. The endoscopy database was searched for endoscopies in the previous 3 years and the Trust Patient Pathway Manager reviewed for possible delays to diagnosis. Patients were classified into &lt;1 month (m) from most recent endoscopy (delay not significant) and &gt;1 m (possible significant delay). Previous biopsies were reviewed by a consultant histopathologist. <h3>Results</h3> 211 cases of UGI cancers were detected (range 25–94 years, mean 70 years, 1.89:1 M:F) representing malignancy in 6.1% of 3460 endoscopies with gastric/oesophageal biopsy. Excluded from further study were: no endoscopy report (13); follow-up of previous diagnosis (38); not primary adenocarcinoma (12). 16/148 (10.8%) cases had had endoscopy within the last 3 years, 6/16 (37.5%) had repeat endoscopy within 1m (mean delay 16.2 days). Reasons included: (2) suspicious endoscopy without histological confirmation of malignancy, (1) previous failed intubation, (1) follow-up of oesophageal ulcer. Of the 10 cases with previous endoscopy &gt;1 m earlier, preventable delays were identified in six cases: Bleeding GU not biopsied at index endoscopy (42 days); failure to biopsy GOJ nodule due to triple anti-platelet therapy (91 days); a patient with known High Grade Dysplasia awaiting cardiology opinion before repeat under general anaesthetic (192 days); delayed surveillance interval for Barrett9s Oesophagus (1035 days from previous endoscopy). Only in two cases was the cancer likely to have been missed on the first endoscopy: delayed follow-up after EMR, synchronous gastric carcinoma in separate site (180 days) and repeat endoscopy for symptomatic dysphagia (SCC in high oesophagus) (526 days). The other 4 cases had endoscopies unrelated to the subsequent diagnosis more than 2 years earlier and the delay was considered unavoidable. Review of previous biopsies, including further stains, showed that no malignant diagnosis had been missed. <h3>Conclusion</h3> 6/148 (4.1%) patients had significant potentially avoidable delays to diagnosis of upper GI cancer. This is commensurate with audits in other centres. Most delays are systematic problems with bookings and appointments rather than endoscopic misses. We believe this simple rolling audit should be adopted as a mandatory Quality Assessment tool for MDTs and/or endoscopy units in order to improve delays in the diagnosis of UGI cancer in all hospitals. <h3>Competing interests</h3> None declared.
A DISORDER OF BLOOD COAGULATION IN SYSTEMIC LUPUS ERYTHEMATOSUS 12
Authors: Stanley L. Lee, Martin Sanders, Helen M. Kahny
Journal: Journal of Clinical Investigation (1955)

Conley and Hartmann (1, 2) have reported the existence of a disorder of blood clotting in two patients with systemic lupus erythematosus.In both cases there were severe hemorrhagic symp- toms associated with prolongation of the clotting time and the presence of a substance interfering with the interaction of thromboplastin and pro- thrombin.Previous studies in this laboratory (3) had suggested that the L. E. cell factor required throm- boplastin or some component thereof, in order to act on leukocytes.A possible relationship between these two sets of data suggested itself: the L. E. cell factor, re- acting in some way with thromboplastin, could inhibit thromboplastin in turn from reacting with prothrombin.If this hypothesis were valid, every blood containing the L. E. cell factor should show impaired thromboplastin function.The clotting disorder described might thus be a char- acteristic feature of systemic lupus.To test this hypothesis, a systematic survey of blood coagulation in every available patient with systemic lupus erythematosus was undertaken. MATERIALS AND METHODSForty-three consecutive patients with systemic lupus erythematosus were studied.Most of these were from the Wards and the Out-Patient Department of The Mount Sinai Hospital; some were private patients or patients in other hospitals.3
Chronic intestinal pseudo-obstruction: how important is JC virus infection?
Authors: G. Lindberg
Journal: Gut (2008)

Adult acquired chronic intestinal pseudo-obstruction (CIP) has mainly been attributed to secondary forms of pseudo-obstruction associated with systemic inflammatory disorders such as progressive systemic sclerosis and systemic lupus erythematosus, endocrine disorders and neurological disorders. However, recent case series from large tertiary centres have described adults without any known predisposing disease, so-called idiopathic CIP.1 2 In this issue of Gut , Selgrad et al ( see page 25 )3 report their findings of JC (John Cunningham) virus proteins in glial cells of the myenteric plexus in 7/10 adult patients with idiopathic CIP. These findings seem to implicate a role for JC virus, a DNA virus that belongs to the family of polyomaviruses, in the pathogenesis of CIP.

JC virus is the causative agent in progressive multifocal leucoencephalopathy (PML),4 a disease that almost exclusively occurs in immnocompromised patients. Today HIV/AIDS is the most prevalent state of deficient cell-mediated immunity associated with a risk for developing PML. In recent years PML has also occurred in patients treated with certain biological drugs such as natalizumab, an antibody against the cellular adhesion molecule α4-integrin, and rituximab, an antibody against the cluster of differentiation 20 (CD20), which is widely expressed on the surface of B cells.5 Reactivation of a latent JC virus infection is believed to be the main mechanism by which the virus ultimately can …
PROTECTIVE EFFECT OF ISCHEMIC PRECONDITIONING ON ISCHEMIA/REPERFUSION INDUCED MICROVASCULAR OBSTRUCTION DETERMINED BY ON-LINE MEASUREMENTS OF CORONARY PRESSURE AND BLOOD FLOW IN PIGS
Authors: Mariann Gyongyosi, Aniko Posa, Rayyan Hemetsberger, Zsolt Petrasi, Ors Petnehazy, Kurt Huber, Dietmar Glogar
Journal: Journal of the American College of Cardiology (2010)
Outcome of acute hepatitis C is related to virus-specific CD4 function and maturation of antiviral memory CD8 responses
Authors: Simona Urbani, Barbara Amadei, Paola Fisicaro, Daniela Tola, Alessandra Orlandini, Luca Sacchelli, Cristina Mori, Gabriele Missale, Carlo Ferrari
Journal: Hepatology (2006)

A timely, efficient, and coordinated activation of both CD4 and CD8 T cell subsets following HCV infection is believed to be essential for HCV control. However, to what extent a failure of the individual T cell subsets can contribute to the high propensity of HCV to persist is still largely undefined. To address this issue, we analyzed the breadth, vigor, and quality of CD4 and CD8 responses simultaneously with panels of peptides covering the entire HCV sequence or containing the HLA-A2–binding motif, and with recombinant HCV proteins in 16 patients with acute HCV infection by tetramer staining, ELISPOT, and intracellular cytokine staining for interferon γ, interleukin (IL)-2, IL-4, and IL-10. Our results indicate that at clinical onset, CD8 responses are similarly weak and narrowly focused in both self-limited and chronically evolving infections. At this stage, CD4 responses are deeply impaired in patients with a chronic outcome as they are weak and of narrow specificity, unlike the strong, broad and T helper 1–oriented CD4 responses associated with resolving infections. Only patients able to finally control infection show maturation of CD8 memory sustained by progressive expansion of CD127+ CD8 cells. Thus, a poor CD8 response in the acute stage of infection may enhance the overall probability of chronic viral persistence. In conclusion , the presence of functional CD4 responses represents one of the factors dictating the fate of infection by directly contributing to control of the virus and by promoting maturation of protective memory CD8 responses.
Mechanism of free fatty acid-induced insulin resistance in humans.
Authors: M Roden, T B Price, G Perseghin, K F Petersen, D L Rothman, G W Cline, G I Shulman
Journal: Journal of Clinical Investigation (1996)

To examine the mechanism by which lipids cause insulin resistance in humans, skeletal muscle glycogen and glucose-6-phosphate concentrations were measured every 15 min by simultaneous 13C and 31P nuclear magnetic resonance spectroscopy in nine healthy subjects in the presence of low (0.18 +/- 0.02 mM [mean +/- SEM]; control) or high (1.93 +/- 0.04 mM; lipid infusion) plasma free fatty acid levels under euglycemic (approximately 5.2 mM) hyperinsulinemic (approximately 400 pM) clamp conditions for 6 h. During the initial 3.5 h of the clamp the rate of whole-body glucose uptake was not affected by lipid infusion, but it then decreased continuously to be approximately 46% of control values after 6 h (P < 0.00001). Augmented lipid oxidation was accompanied by a approximately 40% reduction of oxidative glucose metabolism starting during the third hour of lipid infusion (P < 0.05). Rates of muscle glycogen synthesis were similar during the first 3 h of lipid and control infusion, but thereafter decreased to approximately 50% of control values (4.0 +/- 1.0 vs. 9.3 +/- 1.6 mumol/[kg.min], P < 0.05). Reduction of muscle glycogen synthesis by elevated plasma free fatty acids was preceded by a fall of muscle glucose-6-phosphate concentrations starting at approximately 1.5 h (195 +/- 25 vs. control: 237 +/- 26 mM; P < 0.01). Therefore in contrast to the originally postulated mechanism in which free fatty acids were thought to inhibit insulin-stimulated glucose uptake in muscle through initial inhibition of pyruvate dehydrogenase these results demonstrate that free fatty acids induce insulin resistance in humans by initial inhibition of glucose transport/phosphorylation which is then followed by an approximately 50% reduction in both the rate of muscle glycogen synthesis and glucose oxidation.
Impact of bile duct injury after laparoscopic cholecystectomy on quality of life: a longitudinal study after multidisciplinary treatment
Authors: P. de Reuver, M. Sprangers, E. Rauws, J. Lameris, O. Busch, T. van Gulik, D. Gouma
Journal: Endoscopy (2008)

See also: Commentaire de travail de P. R. de Reuver et al., pp. 637Endoscopy 2008; 40(08): 796-797DOI: 10.1055/s-0032-1306858
Book Review The Flight from Science and Reason (Annals of the New York Academy of Sciences. Vol. 775.) Edited by Paul R. Gross, Norman Levitt, and Martin W. Lewis. 591 pp. New York, New York Academy of Sciences, 1996. $95 (cloth); $95 (paper). 1-57331-002-6 (cloth); 1-57331-003-4 (paper).
Authors: Alfred Tauber
Journal: New England Journal of Medicine (1997)
Gene therapy in inflammatory diseases.
Authors: M SCHNEIDER
Journal: Annals of the Rheumatic Diseases (2001)

Gene therapy in inflammatory diseases. Eds Christopher H Evans and Paul D Robbins. (Pp 272; $95.) Basel: Birkhauser, 2000. ISBN 0-8176-5855-6.

Gene Therapy In Inflammatory Diseases aims at giving readers an overview of gene therapy, being a collection of authoritative reviews of selected research projects. The reader will find a series of interesting topics in gene therapy, showing data from preclinical …
Plain packaging for tobacco products
Authors: D. C. Currow, A. Dessaix
Journal: BMJ (2011)

Minimising the emotional attachment to a cigarette brand could help smokers quit

On 7 April 2011, the minister for health and ageing, Nicola Roxon, introduced legislation into the Australian parliament to mandate plain packaging for all tobacco products in Australia. Australia is the first jurisdiction to introduce such legislation, and—in keeping with previous initiatives—the programme will be evaluated prospectively to assess the contribution it makes to the community’s smoking rates.

Smoking rates in Australia have declined over the past three decades as a result of progressively stronger tobacco control measures (box) and a concomitant change in behavioural norms. For example, today only 5% of non-smokers are exposed to smoking inside their homes.1 Adult daily smoking rates in Australia in 2010 were 15% compared with 24% in 1991. However, Aboriginal and Torres Strait Islander people are twice as likely to smoke as non-indigenous Australians. People living in remote or very remote areas are almost twice as likely to smoke as those in major cities, and those in the most disadvantaged fifth of the population are more than twice as likely to smoke as those in the least disadvantaged fifth.1 …
Autologous stem cell transplantation in adults with acute lymphoblastic leukemia in first complete remission: analysis of the LALA-85, -87 and -94 trials
Authors: N Dhédin, H Dombret, X Thomas, V Lhéritier, J-M Boiron, F Rigal-Huguet, N Vey, M Kuentz, O Reman, F Witz, A Delannoy, T Kovacsovics, K Bradstock, C Charrin, C Boucheix, J Gabert, D Blaise, D Fière, J-P Vernant
Journal: Leukemia (2005)
Single photon emission computed tomography with technetium-99m hexakis 2-methoxyisobutyl isonitrile in acute myocardial infarction before and after thrombolytic treatment: Assessment of salvaged myocardium and prediction of late functional recovery
Authors: Giovanni Maria Santoro, Gianni Bisi, Roberto Sciagrà, Mario Leoncini, Pier Filippo Fazzini, Ugo Meldolesi
Journal: Journal of the American College of Cardiology (1990)
Toluene Habituation
Authors: Richard Satran, Vernon N. Dodson
Journal: New England Journal of Medicine (1963)

IN the past few years, there have been isolated reports describing adults as well as children who have sniffed or inhaled volatile fumes of various organic compounds.1 2 3 4 5 Such behavior is usually directed toward the production of a state of elation or exhilaration; however, headaches, dizziness and unconsciousness may result. Since intoxications of this type are rather unusual, it seems worthwhile to describe in detail the case of a patient who inhaled toluene vapor with regularity for a period of ten years.Case ReportA 30-year-old married man was admitted to the University Hospital in February, 1961, because of recurrent headaches . . .
GASOLINE AND KEROSENE POISONING IN CHILDREN
Authors: JOHN A. NUNN
Journal: JAMA (1934)

This article comprises a summary of the clinical and laboratory examinations in seven cases of gasoline poisoning and sixty-five cases of kerosene poisoning in children admitted to the Robert B. Green Memorial Hospital between October 1931 and July 1933. The ages ranged from 10 months to 4 years. A considerable number of children have been brought to the emergency room of the hospital with a history of having taken one or the other of these petroleum products. Only those showing signs of acute poisoning, however, were admitted to the hospital. Those showing very little evidence of acute poisoning were allowed to return to their homes after treatment consisting of gastric lavage and a laxative. The essentials of several of the cases are herewith reported. <h3>REPORT OF CASES</h3><h3>Case 1.—</h3> A boy, aged 14 months, Mexican, was admitted in a stuporous condition. He had swallowed a "small amount" of gasoline about
Metabolic studies of radioiodinated serum amyloid P component in normal subjects and patients with systemic amyloidosis.
Authors: P N Hawkins, R Wootton, M B Pepys
Journal: Journal of Clinical Investigation (1990)

125I-Serum amyloid P component (SAP), injected intravenously into 10 normal subjects, remained predominantly intravascular with mean (SD) T1/2 (half time) in plasma of 24.5 (5.9) h. The fractional catabolic rate of 68 (19)% of the plasma pool per day was more rapid than other reported human plasma proteins. All radioactivity was excreted in the urine by 14 d. In 16 patients with monoclonal gammopathy or chronic inflammatory diseases, but without amyloidosis, 125I-SAP metabolism was normal. However, among 45 patients with biopsy-proven systemic amyloidosis (25, amyloid A type; 20, amyloid L type), 125I-SAP was cleared from the plasma more rapidly, accumulated in the amyloid deposits, and persisted there. The T1/2 in amyloid, measured directly with 131I-SAP, was 24 d. Repeat studies after 6-18 mo were notably consistent in normals but changed significantly in amyloid patients, generally correlating with clinical signs of disease progression. Measurements of 125I-SAP turnover may thus be of value for diagnosis and monitoring of amyloidosis. Analysis of SAP metabolism in amyloidosis suggests that plasma SAP is in dynamic equilibrium with a very large amyloid pool, and in two autopsies the total mass of SAP in the amyloid deposits was 2,100 and 21,000 mg, respectively.