tbuckley/cabot-search huggingface dataset:
BMI1 and Mel-18 oppositely regulate carcinogenesis and progression of gastric cancer
Authors: Xiao-Wei Zhang, Ya-Ping Sheng, Qian Li, Wei Qin, You-Wei Lu, Yu-Fan Cheng, Bing-Ya Liu, Feng-Chun Zhang, Jin Li, Goberdhan P Dimri, Wei-Jian Guo
Journal: Molecular Cancer (2010)

Abstract Background The BMI1 oncogene is overexpressed in several human malignancies including gastric cancer. In addition to BMI1, mammalian cells also express Mel-18, which is closely related to BMI1. We have reported that Mel-18 functions as a potential tumor suppressor by repressing the expression of BMI1 and consequent downregulation of activated AKT in breast cancer cells. However, the mechanisms of BMI1 overexpression and the role of Mel-18 in other cancers are still not clear. The purpose of this study is to investigate the role of BMI1 and Mel-18 in gastric cancer. Results BMI1 was found to be overexpressed in gastric cancer cell lines and gastric tumors. Overexpression of BMI1 correlated with advanced clinical stage and lymph node metastasis; while the expression of Mel-18 negatively correlated with BMI1. BMI1 but not Mel-18 was found to be an independent prognostic factor. Downregulation of BMI1 by Mel-18 overexpression or knockdown of BMI1 expression in gastric cancer cell lines led to upregulation of p16 (p16INK4a or CDKN2A) in p16 positive cell lines and reduction of phospho-AKT in both p16-positive and p16-negative cell lines. Downregulation of BMI1 was also accompanied by decreased transformed phenotype and migration in both p16- positive and p16-negative gastric cancer cell lines. Conclusions In the context of gastric cancer, BMI1 acts as an oncogene and Mel-18 functions as a tumor suppressor via downregulation of BMI1. Mel-18 and BMI1 may regulate tumorigenesis, cell migration and cancer metastasis via both p16- and AKT-dependent growth regulatory pathways.
Evidence for Summation and Voltage Dependency in Rabbit Atrioventricular Nodal Fibers
Authors: DOUGLAS P. ZIPES, CARLOS MENDEZ, GORDON K. MOE
Journal: Circulation Research (1973)

This study demonstrated summation in the rabbit AV node and suggested that the action potential rise time (dV/dt) of nodal cells was voltage dependent. Summation was produced in two ways. (1) The atrium and the floor of the coronary sinus were divided to establish two noncontiguous, anatomically separate atrial inputs to the AV node. Conduction to the His bundle occurred when both sides of the atrium were stimulated simultaneously at premature cycle lengths which produced local responses in the N region when either side was stimulated individually. (2) With the atrium intact, the atrium and the His bundle were stimulated together at intervals which allowed the simultaneous arrival of the advancing wave fronts at the impaled N cell. This collision resulted in an N action potential which occurred slightly earlier and had an increased dV/dt and amplitude, suggesting that the nodal cells tested, as well as other cardiac cells, were voltage dependent. Further evidence was provided by the influence of the N region on nodal action potential contours according to the direction of propagation. During orthograde conduction, cells close to N in the AN region had a larger dV/dt and cells in the NH region had a smaller dV/dt than these respective cells had during retrograde conduction. Since dV/dt is a major determinant of conduction velocity, during orthograde conduction rapid conduction within the AN region but relatively slow conduction where N cells supply excitatory current to NH cells occurred. In the retrograde direction, conduction from the His bundle to the midnodal region was prompt, but deceleration occurred where the N region feeds the upper nodal cells.
Microbial Keratitis in Childhood
Authors: Oscar A. Cruz, Smeena M. Sabir, Hilda Capo, Eduardo C. Alfonso
Journal: Ophthalmology (1993)

Background: Microbial keratitis occurs infrequently in childhood. The leading ocular predisposing factors are trauma and preexisting corneal disease. Many of the agerelated risk factors in adults play a minor role in children. Methods: The authors retrospectively studied 51 eyes with ulcerative keratitis in 50 children younger than 16 years of age. This includes all patients treated at Bascom Palmer Eye Institute during an 11 1/2-year period from January 1, 1980, to June 30, 1991. The criterion for inclusion in the study was a discharge diagnosis of microbial (nonviral) keratitis. Results: The principal risk factors identified in this study were trauma (44%), prior corneal surgery (24%), systemic illness (14%), and contact lens wear (12%). Systemic illness or an immunocompromised state existed in 7 (47%) of the 15 children younger than 3 years of age. There was a large male preponderance (68%). Forty-four (86.3%) of the 51 eyes were culture-positive; six (11.7%) were polymicrobial. Five of seven culture-negative patients had received prior topical antibiotic therapy. Pseudomonas aeruginosa (34%), Staphylococcus aureus (20%), and fungi (18%) were the most common organisms isolated. Seven (14%) eyes required surgery. Conclusion: This study presents important differentiating factors between adult and childhood nonviral microbial keratitis. Identification of principal risk factors in children may aid in early recognition and treatment of microbial keratitis. Background: Microbial keratitis occurs infrequently in childhood. The leading ocular predisposing factors are trauma and preexisting corneal disease. Many of the agerelated risk factors in adults play a minor role in children. Methods: The authors retrospectively studied 51 eyes with ulcerative keratitis in 50 children younger than 16 years of age. This includes all patients treated at Bascom Palmer Eye Institute during an 11 1/2-year period from January 1, 1980, to June 30, 1991. The criterion for inclusion in the study was a discharge diagnosis of microbial (nonviral) keratitis. Results: The principal risk factors identified in this study were trauma (44%), prior corneal surgery (24%), systemic illness (14%), and contact lens wear (12%). Systemic illness or an immunocompromised state existed in 7 (47%) of the 15 children younger than 3 years of age. There was a large male preponderance (68%). Forty-four (86.3%) of the 51 eyes were culture-positive; six (11.7%) were polymicrobial. Five of seven culture-negative patients had received prior topical antibiotic therapy. Pseudomonas aeruginosa (34%), Staphylococcus aureus (20%), and fungi (18%) were the most common organisms isolated. Seven (14%) eyes required surgery. Conclusion: This study presents important differentiating factors between adult and childhood nonviral microbial keratitis. Identification of principal risk factors in children may aid in early recognition and treatment of microbial keratitis.
A prognostic score for acute graft-versus-host disease based on biomarkers: a multicentre study
Authors: John E Levine, Thomas M Braun, Andrew C Harris, Ernst Holler, Austin Taylor, Holly Miller, John Magenau, Daniel J Weisdorf, Vincent T Ho, Javier Bolaños-Meade, Amin M Alousi, James L M Ferrara
Journal: The Lancet Haematology (2014)
Is animal research sufficiently evidence based to be a cornerstone of biomedical research?
Authors: P. Pound, M. B. Bracken
Journal: BMJ (2014)

Public acceptance of the use of animals in biomedical research is conditional on it producing benefits for humans. <b>Pandora Pound</b> and <b>Michael Bracken</b> argue that the benefits remain unproved and may divert funds from research that is more relevant to doctors and their patients
Role of alveolar epithelial ICAM-1 in lipopolysaccharide-induced lung inflammation
Authors: B. Beck-Schimmer, C. Madjdpour, S. Kneller, U. Ziegler, T. Pasch, R.P. Wüthrich, P.A. Ward, R.C. Schimmer
Journal: European Respiratory Journal (2002)

Intercellular adhesion molecule-1 (ICAM-1) is known to play a central role in lung inflammation. Limited information, however, is available regarding the expression and biological function of ICAM-1 in the alveolar epithelial compartment. The current report analyses the expression pattern of ICAM-1 in primary cultures of rat alveolar epithelial cells (AECs) and in the rat lung following instillation of bacterial endotoxin (lipopolysaccharide (LPS)) in order to better define the role of alveolar epithelial ICAM-1. AECs stimulated in vitro with LPS were evaluated for ICAM-1 and ICAM-1 messenger ribonucleic acid content. Adherence assays with neutrophils and macrophages were performed. Endotoxin-induced ICAM-1 upregulation on AECs was demonstrated in vivo by immunofluorescence staining. In addition, the effect of intratracheally-instilled anti-ICAM-1 was assessed. Significant upregulation of ICAM-1 occurred in vitro and in vivo on AECs after LPS stimulation. Adherence assays showed a 114% increase in adhesion of neutrophils to AECs. Antibody directed against ICAM-1 reduced this adhesion by 40%. A significant reduction in the number of neutrophils in bronchoalveolar lavage fluid and whole lung was seen under airway ICAM-1 blockade. These data indicate that intercellular adhesion molecule-1 participates in the inflammatory response to lipopolysaccharide-induced lung injury in the distal airways by interacting mainly with neutrophils.
Computed tomographic colonography versus barium enema for diagnosis of colorectal cancer or large polyps in symptomatic patients (SIGGAR): a multicentre randomised trial
Authors: Steve Halligan, Kate Wooldrage, Edward Dadswell, Ines Kralj-Hans, Christian von Wagner, Rob Edwards, Guiqing Yao, Clive Kay, David Burling, Omar Faiz, Julian Teare, Richard J Lilford, Dion Morton, Jane Wardle, Wendy Atkin
Journal: The Lancet (2013)
Identification of <i>KIF5B-RET</i> and <i>GOPC-ROS1</i> Fusions in Lung Adenocarcinomas through a Comprehensive mRNA-Based Screen for Tyrosine Kinase Fusions
Authors: Yoshiyuki Suehara, Maria Arcila, Lu Wang, Adnan Hasanovic, Daphne Ang, Tatsuo Ito, Yuki Kimura, Alexander Drilon, Udayan Guha, Valerie Rusch, Mark G. Kris, Maureen F. Zakowski, Naiyer Rizvi, Raya Khanin, Marc Ladanyi
Journal: Clinical Cancer Research (2012)

Abstract Background: The mutually exclusive pattern of the major driver oncogenes in lung cancer suggests that other mutually exclusive oncogenes exist. We conducted a systematic search for tyrosine kinase fusions by screening all tyrosine kinases for aberrantly high RNA expression levels of the 3′ kinase domain (KD) exons relative to more 5′ exons. Methods: We studied 69 patients (including five never smokers and 64 current or former smokers) with lung adenocarcinoma negative for all major mutations in KRAS, EGFR, BRAF, MEK1, HER2, and for ALK fusions (termed “pan-negative”). A NanoString-based assay was designed to query the transcripts of 90 tyrosine kinases at two points: 5′ to the KD and within the KD or 3′ to it. Tumor RNAs were hybridized to the NanoString probes and analyzed for outlier 3′ to 5′ expression ratios. Presumed novel fusion events were studied by rapid amplification of cDNA ends (RACE) and confirmatory reverse transcriptase PCR (RT-PCR) and FISH. Results: We identified one case each of aberrant 3′ to 5′ ratios in ROS1 and RET. RACE isolated a GOPC-ROS1 (FIG-ROS1) fusion in the former and a KIF5B-RET fusion in the latter, both confirmed by RT-PCR. The RET rearrangement was also confirmed by FISH. The KIF5B-RET patient was one of only five never smokers in this cohort. Conclusion: The KIF5B-RET fusion defines an additional subset of lung cancer with a potentially targetable driver oncogene enriched in never smokers with “pan-negative” lung adenocarcinomas. We also report in lung cancer the GOPC-ROS1 fusion originally discovered and characterized in a glioma cell line. Clin Cancer Res; 18(24); 6599–608. ©2012 AACR.
The effect of BiPAP on maximum exercise capacity in patients with COPD
Authors: Ana-Maria Moga, Michel De Marchie, Stéphane Delisle, Jadranka Spahija
Journal: European Respiratory Journal (2011)

Background: Noninvasive ventilation has been used as an adjunct to exercise. The aim of this study was to evaluate the effect of BiPAP (Vision, Respironics; no Plateau Exhalation Valve), compared to no assist, on maximum exercise capacity in individuals with COPD.

Methods: A randomized crossover design was used. Ten stable COPD patients (FEV1 53±21% pred) performed three symptom-limited incremental exercise tests on a bicycle ergometer while breathing through a mouthpiece, with either no pressure support (PSno), PS of 0 cm H2O (PS0; IPAP & EPAP 4 cm H2O) or 10 cm H2O (PS10; IPAP 14 & EPAP 4 cm H2O) of assist on separate days. Exercise workload (WL), dyspnea and leg effort (Borg), end-expiratory lung volume (EELV), breathing pattern, O2 uptake (VO2) and CO2 production (VCO2) were measured during exercise.

Results: Peak WL was lower with PS10 (33±16) and PS0 (30.5±13) than PSno (43±19) (p<0.001); there was no difference between PS0 and PS10. Dyspnea at peak exercise was similar with PSno, PS0 and PS10; at isoload it was lower with PSno compared to PS10 and PS0 (p<0.01). Leg effort at peak exercise was higher with PSno than PS10 and PS0 (p<0.05), whereas it was not different at isoload. Tidal volume (VT) and minute ventilation (VE) were highest with PS10 and lowest with PSno both at peak exercise (p<0.001) and isoload (p<0.001). EELV was similar at peak exercise with all three conditions. VO2 and VCO2 were greater with PS10 and PS0 than PSno (both p<0.001), both at peak exercise and isoload.

Conclusion: Use of BiPAP during incremental exercise in the absence of a plateau exhalation valve increases VT and VE at the expense of increasing the VO2 and dyspnea, which in turns reduces peak exercise WL in COPD patients.
Proliferative retinopathy and nephropathy at presentation in young insulin dependent diabetics.
Authors: J A O'Hare
Journal: BMJ (1990)

RelatIve ri'sk (95{)#n confidence interval) of breast cancer after term birth calcuilated from 422 women with breast canicer (cascs) anid 44 7 ci)ontrols by aige grouip Age 40Age [40][41][42][43][44][45][46][47][48][49] All women 120 cases, 117 controls) (302 cases, 330 controls) (422 cases, 447 controls)No of vears since la.t termii birth*:--1 lo I t lo(ot lO-Ot 7-0) 54 0-021 to 1-42) 088 0047 to 1 64) 0 80 (0 48 to 1-32)3-11'4.,0 41 to 3 20) 1-35 )0 57 to 3 20) 1-44 (0-80 to 2-61) 3 A 1-96(0 053 to 7-27) 855 (1 00 to 2-92(1-32to649)for trend 187 (p=0 172) 1-90(p=0 168) 5 -30(p=0021) Agc ycars) at first term birthT:-2( 1-()Ot l 00t l OOt 21-158(0-65to 385) CommentBoth patients had proliferative diabetic retinopathy, diabetic polyneuropathy, and early nephropathy.Proliferative diabetic retinopathy in type I diabetes rarely develops until the diabetes has been present for
Ultrasound assessment of spleen size in collegiate athletes
Authors: R G Hosey, C G Mattacola, V Kriss, T Armsey, J D Quarles, J Jagger
Journal: British Journal of Sports Medicine (2006)

Objectives: To determine normal spleen dimensions in a healthy collegiate athletic population. Methods: 631 Division I collegiate athletes from one university participated in the study. During pre-participation examinations, demographic data collected were collected from volunteer athletes including sex, race, measurement of height and weight, and age. Subjects also completed a medical history form to determine any history of mononucleosis infection, platelet disorder, sickle cell disease (or trait), thalassaemia, or recent viral symptoms. Subjects then underwent a limited abdominal ultrasound examination, where splenic length and width were recorded. Results: Mean (SD) splenic length was 10.65 (1.55) cm and width, 5.16 (1.21) cm. Men had larger spleens than women (p&lt;0.001). White subjects had larger spleens than African-American subjects (p&lt;0.001). A previous history of infectious mononucleosis or the presence of recent cold symptoms had no significant affect on spleen size. In more than 7% of athletes, baseline spleen size met current criteria for splenomegaly. Conclusions: There is a wide range of normal spleen size among collegiate athletes. Average spleen size was larger in men and white athletes than in women and black athletes. A single ultrasound examination for determination of splenomegaly is of limited value in this population.
A Person-Centred Approach to Communicating Risk
Authors: Andy Alaszewski
Journal: PLoS Medicine (2005)

Doctors and other health professionals play a key role in communicating risk information. They are advisers to patients, especially when patients have to make fateful decisions that can irrevocably change their lives. There is a developing body of literature on the ways in which risk information can be effectively communicated [1,2]. However, much of this literature focuses on the nature of risk information and ways in which the transfer of this information can be improved. It does not fully take into account the complexity of the real world of clinical practice, nor the importance of considering patients as active partners in communication.
A comparison of incidence of colorectal cancer and polyps in bowel cancer screening programme patients with symptomatic patients referred under 2 week wait in a demographically matched population
Authors: P. Harrow, S. Nayagam, N. Stafford, K. Hopkins, R. Loke
Journal: Gut (2011)

<h3>Introduction</h3> Traditionally the majority of colorectal cancer has been diagnosed following investigations triggered by symptoms suggestive of malignancy. The National Bowel Cancer Screening Programme has created an alternative route to diagnosis of asymptomatic individuals. <h3>Methods</h3> This prospective study compared the incidence of colorectal cancer and adenomatous polyps at colonoscopy and virtual colonoscopy in a population demographically matched for age (60–70) and geographical area (limited to 33 local GP practices). Subjects were either asymptomatic under the Bowel Cancer Screening Programme (BCSP) or symptomatic patients referred under the 2 week wait target (2ww). All endoscopy took place at the Kent &amp; Sussex Hospital between August 2009 and August 2010. Data from colonoscopy reports and histology were analysed. <h3>Results</h3> 155 BCSP (mean age 66.0, 61% male) and 127 2ww patients (mean age 64.6, 40% male) fulfilled the entry criteria. Sub-group analysis of both gender groups also found a significant difference in the incidence of adenomatous polyps and no significant difference in the incidence of malignancy. <h3>Conclusion</h3> This study demonstrates comparable incidence of colorectal cancers in the two groups. The incidence of polyps was significantly higher in the BCSP group and importantly the polyps found in BCSP were of higher risk of progression to cancer according to the classical adenoma-carcinoma sequence.1 This study demonstrates the efficacy of the BCSP at detecting significant colorectal pathology. The detection of colorectal cancer and high risk polyps are thought to reduce mortality from colorectal cancer.2 The similar detection rates between the symptomatic and asymptomatic groups highlights the poor positive predictive value of symptoms and the assessment currently used for emergency referrals for the diagnosis of colorectal cancer.
Double-blind, placebo-controlled trial of methylphenidate in older, depressed, medically ill patients
Authors: A E Wallace, L L Kofoed, A N West
Journal: American Journal of Psychiatry (1995)

The authors examined the efficacy of methylphenidate in the treatment of depression in a group of older, medically ill patients.Sixteen patients underwent an 8-day double-blind, randomized, placebo-controlled crossover trial; 13 completed the trial.Statistically and clinically significant treatment responses were found.These results support the use of methylphenidate in older, medically ill patients in whom rapid resolution of depressive symptoms is crucial.
Orbital blowout fractures in sport.
Authors: N P Jones
Journal: British Journal of Sports Medicine (1994)

One-third of orbital blowout fractures are sustained during sport. Soccer is most commonly involved. Though visual acuity recovery is usually complete, permanent loss of binocular visual field is almost universal. Typically high-energy blows by opponent's finger, fist, elbow, knee or boot are responsible. Injuries to the eye itself may also be sustained and should be looked for. Ocular protection may be feasible in some sports, but the main preventive measure to be addressed is the reduction in aggressive play or deliberate injury.
Intracavity suction and drainage in the treatment of emphysematous bullae.
Authors: A M Macarthur, S W Fountain
Journal: Thorax (1977)

Patients with large intrapulmonary emphysematous bullae present a considerable therapeutic problem, particularly if their respiratory reserve is low, because of the risks of open operation. The method of draining intrapulmonary cavities, pioneered by Monaldi for the treatment of tuberculosis, is here described as applied to emphysematous bullae. Thirty-one patients were treated by intracavity suction and drainage. There were two operative deaths (6.5%). Apart from infection, no other significant postoperative complications ensued. Radiographic improvement occurred in all patients but one (96.7%). Where forced expiratory volume in one second and vital capacity were measured improvement was obtained in five out of six patients. Symptomatic improvement, which generally corresponded well to improvement in respiratory function tests, occurred in 28 patients (90.3%), all but one of whom survived.
Determination of peak expiratory flow
Authors: S Kano, DL Burton, CJ Lanteri, PD Sly
Journal: European Respiratory Journal (1993)

It is still unknown whether peak expiratory flow (PEF) is determined by "wave speed" flow limitation in the airways. To investigate the influences of airway mechanical properties on PEF, five healthy adults performed maximal forced expiratory effort (MFEE) manoeuvres, in the standard manner and following breathholds at total lung capacity (TLC) of 2 s and 10 s. Oesophageal pressure (Poes) was measured as an index of respiratory effort. Subjects also performed a MFEE following a 10 s breathhold during which intrathoracic pressure was voluntarily raised by a Valsalva manoeuvre, which would increase transmural pressure and cross-sectional area of the extrathoracic airway. Additional MFEEs were performed with the neck fully flexed and extended, to change longitudinal tracheal tension. In separate studies, PEF was measured with a spirometer and with a pneumotachograph. Breathholds at TLC (2 s and 10 s), and neck flexion reduced PEF by a mean of 9.8% (SD 2.9%), 9.6% (SD 1.6%), and 8.7% (SD 2.8%), respectively, when measured with the spirometer. The same pattern of results was seen when measured with the pneumotachograph. These reductions occurred despite similar respiratory effort. Voluntarily raising intrathoracic pressure during a 10 s breathhold did not reverse a fall in PEF. MFEE manoeuvre with neck extension did not result in an increase in PEF, the group mean % changes being -3.0% (SD 5.0%). We conclude that these results do not allow the hypothesis that "wave-speed" (Vws) is reached at PEF to be rejected. A breathhold at TLC could increase airway wall compliance by allowing stress-relaxation of the airway, thus reducing the "Vws" achievable.