tbuckley/cabot-search huggingface dataset:
T cell recognition of an HLA-A2-restricted epitope derived from a cleaved signal sequence.
Authors: M Guéguen, W E Biddison, E O Long
Journal: The Journal of Experimental Medicine (1994)

An alternative pathway for class I-restricted antigen presentation has been suggested on the basis of peptides bound to HLA-A2 molecules in cells lacking the transporter for antigen presentation (TAP). Most of these peptides were derived from signal sequences for translocation into the endoplasmic reticulum (ER). However, it is not known whether these peptides can be presented to T cells. The hydrophobic nature of an HLA-A2-restricted T cell epitope (M1 58-66) was exploited to test whether it could be presented to T cells when derived from a signal sequence. Replacing the signal sequence of the influenza virus hemagglutinin molecule H3 with an artificial sequence containing that HLA-A2-restricted T cell epitope resulted in efficient translocation of H3 molecules into the ER and transport to the cell surface. This signal sequence-derived epitope was presented to HLA-A2-restricted T cells. Involvement of cytosolic processing for this presentation is very unlikely, because (a) presentation occurred in cells lacking TAP; (b) expression of H3 molecules with the artificial signal sequence did not produce a detectable cytosolic form of H3; and (c) presentation of the same epitope expressed in cytosolic forms of antigen required TAP. Thus, a peptide derived from a signal sequence cleaved in the ER can provide an epitope for HLA-A2-restricted T cell recognition.
766 ASSOCIATION BETWEEN THE PSC SUSCEPTIBILITY VARIANT IN THE MST1 LOCUS AND CHOLANGIOCARCINOMA RISK: CASE-CONTROL ANALYSIS OF A LARGE EUROPEAN COHORT
Authors: M. Krawczyk, A. Hoblinger, F. Mihalache, M. Acalovschi, F. Lammert, V. Zimmer
Journal: Journal of Hepatology (2012)
S121 Mediator profiling of severe asthma phenotypes
Authors: D. Desai, C. J. Newby, P. Haldar, S. Shah, S. Gupta, M. Bafadhel, A. Singapuri, S. Siddiqui, J. Woods, A. Herath, I. K. Anderson, P. Bradding, R. H. Green, A. J. Wardlaw, I. D. Pavord, R. D. May, C. E. Brightling
Journal: Thorax (2011)

<h3>Background</h3> Severe asthma is a heterogeneous disease. Defining its phenotypic heterogeneity is likely to shed light upon its immunopathogenesis and direct therapy. We sought to determine the relationship between phenotypes of severe asthma and sputum mediator profiles. <h3>Methods</h3> Subjects were recruited from a Difficult Asthma Clinic at a single centre (n=164) and assessments of lung function, atopic status, asthma control and sputum induction were undertaken. Sputum was obtained and supernatants were analysed for 23 mediators using the Meso-Scale Discovery platform. We performed k-means cluster analysis to determine clinical clusters using the baseline characteristics and sputum differential counts. The pattern of mediator expression was determined by factor analysis to identify biological factors. The biological factors were related to the clinical clusters and subjects stratified by asthma control, exacerbation frequency, treatment and sputum cell counts. The repeatability of the individual clinical characteristics and biological mediators was assessed in paired samples in 106 subjects and in three samples in 66 subjects. <h3>Results</h3> We identified four clinical clusters and five biological factors. The biological factors were differentially expressed in subjects stratified by sputum cell counts, asthma control and exacerbation frequency, but were not significantly different across the clinical clusters. The within subject repeatability of mediators was moderate; biological factors were consistent and tracked with sputum cell counts for the repeated visits. <h3>Conclusions</h3> Sputum mediator profiling of severe asthma revealed repeatable biological factors that were strongly associated with cellular profiles and inform our understanding of asthma phenotypes.
Bladder Neoplasms after Nephroureterectomy: does the Surgery of the Lower Ureter, Transurethral Resection or Open Surgery, Influence the Evolution?
Authors: J Salvador-Bayarri, L Rodrı́guez-Villamil, V Imperatore, J Palou Redorta, H Villavicencio-Mavrich, J Vicente-Rodrı́guez
Journal: European Urology (2002)
Abstract 3631: AN019, a potent anticancer agent, suppresses tumors, ErbB-2, and angiogenesis in pancreatic cancer cells
Authors: Christopher S. Gondi, Bharathi Gorantla, A.K.S. Bhujanga Rao, K. Amala, M.U.R. Naidu, K.V. Jogi, G.V. Ramana, M. Praveen Chowdary, Jasti S. Rao
Journal: Cancer Research (2010)

Abstract Epidermal growth factor receptor (EGFR), a member of the HER family of receptor tyrosine kinases, has been identified as a therapeutic target for pancreatic cancer. Excessive ErbB-2 signaling is associated with the development of a wide variety of solid malignancies. In this study, we used the pancreatic cancer cell lines MIA PaCa-2 and PANC-1 to demonstrate the suppressive, anti-angiogenic, and anti-proliferative effects of a novel compound known as AN019. Here, we show that AN019 inhibits the invasiveness of pancreatic cancer cells in a dose-dependent manner and is superior to treatment with Gemcitabine alone. Angiogenic assays demonstrated that AN019 treatment retarded the invasive potential of pancreatic cancer cells and provided greater angiogenic inhibition than Gemcitabine. In addition, western blot analysis demonstrated that AN019 inhibits expression of ErbB-2 in a dose-dependent manner in MIA PaCa-2 and PANC-1 cells. In contrast, Gemcitabine lacked a similar dose response. Finally, the proliferation assay showed that while AN019 retarded proliferation in a dose-dependent manner, Gemcitabine did not. Our in vivo studies showed that expression of ErbB-2 and VEGF decreased in a dose-dependent manner in AN019-treated animals with subcutaneously implanted MIA PaCa-2 tumors. A treatment combination of AN019 and Gemcitabine had an effect similar to that of treatment with AN019 alone, thereby indicating no specific contribution from Gemcitabine. Our results demonstrate AN019 is superior to Gemcitabine, and AN019 is a specific suppressor of ErBB-2 in vitro and in vivo. In addition, AN019 has anti-proliferative and anti-angiogenic properties. Taken together, these results clearly indicate the potential therapeutic use of AN019 as an anti-cancer agent. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 3631.
How valid are the indicators?
Authors: G. A. Gooiker, R. A. E. M. Tollenaar
Journal: BMJ (2010)

Reeves and colleagues explained the rationale behind removing eight performance indicators from the UK Quality and Outcomes Framework.1 But how valid are performance indicators?

In collaboration with the Comprehensive Cancer Centre West in the Netherlands, we tested the validity of tumour positive margin rate after breast conserving surgery for breast neoplasm as an indicator in relation to the used definition (rate of focal involvement, extensive involvement, …
ACUTE KIDNEY INJURY FOLLOWING TRANSCATHETER AORTIC VALVE IMPLANTATION USING BOTH EDWARDS SAPIEN XT AND COREVALVE BIOPROSTHESIS: IMPLEMENTATION OF THE UPDATED VARC–2 CRITERIA
Authors: Ofer Havakuk, Eyal Ben–Assa, Maayan Konigstein, Yigal Abramowitz, Arie Steinvil, Eran Leshem–Rubinow, Amir Halkin, Gad Keren, Shmuel Banai, Ariel Finkelstein
Journal: Journal of the American College of Cardiology (2013)
Glycine-induced hyponatremia in the rat: A model of post-prostatectomy syndrome
Authors: Stephen M. Silver, Shari A. Kozlowski, Jane E. Baer, Susannah J. Rogers, Richard H. Sterns
Journal: Kidney International (1995)

Post-prostatectomy syndrome (PPS) is characterized by hyponatremia after absorption of glycine irrigant. To study the pathogenesis of this syndrome, adult male rats with ligated ureters were infused over 15 minutes with 7.5 ml/100 g body weight of isosmotic glycine (N = 9) or mannitol (N = 9) and were compared to non-infused, ureter-ligated controls (N = 9). Immediately post-infusion, plasma sodium had decreased similarly in glycine- and mannitol-infused animals (111 +/- 2 vs. 106 +/- 1 mmol/liter), but plasma osmolality remained at control levels in both groups (285 +/- 1 vs. 288 +/- 1 mOsm/kg). Two hours post-infusion, hyponatremia was stable in the mannitol group (108 +/- 1 mmol/liter), but in the glycine group plasma sodium increased significantly (to 120 +/- 1 mmol/liter). Plasma osmolality two hours post-infusion was maintained in both the glycine (287 +/- 2) and mannitol (292 +/- 2) groups. Brain water in glycine-infused animals (3.90 +/- 0.01 liter/kg dry wt) was not significantly different from the mannitol-infused group (3.85 +/- 0.01) and only 1.8% higher than non-infused controls (3.83 +/- 0.02). Brain tissue glycine did not differ between the three groups. In contrast, muscle water two hours post-infusion in the glycine group was 6% higher than mannitol-infused and 13% higher than non-infused animals. Muscle glycine content in the glycine group (67 +/- 4 mM/kg dry tissue) was increased when compared to both mannitol-infused (25 +/- 1) and non-infused (20 +/- 1) groups.(ABSTRACT TRUNCATED AT 250 WORDS)
Screening for Cystic Fibrosis
Authors: Harvey R. Colten
Journal: New England Journal of Medicine (1990)

Cystic fibrosis is a chronic disease of children and increasingly of adults; one third of the more than 15,000 patients listed in the registry of the North American National Cystic Fibrosis Foundation are older than 21 years. Respiratory complications account for much of the morbidity and more than 95 percent of the mortality from cystic fibrosis, although exocrine-gland dysfunction in many other organ systems affects all patients to a greater or lesser degree. Each year nearly 40 percent of those with cystic fibrosis are hospitalized at least once for a week or more. These episodes and the cost of outpatient . . .
Preventing overdiagnosis: the myth, the music, and the medical meeting
Authors: Ray Moynihan
Journal: BMJ (2015)

Registrations and abstracts are now open for the third Preventing Overdiagnosis conference



Uncertainty, conflict, and controversy: the life blood of science now flows freely through the growing global debate about the problem of overdiagnosis and how to prevent it. This month a Harvard radiologist was reported attacking overdiagnosis as a “myth,” The BMJ launched a digital theme issue on the topic, and a Canadian professor put the finishing touches to a short music video on overdiagnosis, which is likely to go viral. After successful sell-out gatherings in Dartmouth College, New Hampshire, in 2013 and Oxford in 2014, seats are starting fill for the next international Preventing Overdiagnosis scientific meeting (www.preventingoverdiagnosis.net). Supported by The BMJ , the conference takes place this year in September inside the heart of the US medical establishment, at the publicly funded National Institutes of Health, just outside Washington, DC.

The Harvard professor Daniel Kopans was quoted in the online Cancer Network publication arguing, “Overdiagnosis is a myth that has been created by a handful of individuals who provide no care for women with breast cancer.”1 A strong voice …
A Phase I Pharmacokinetic and Pharmacodynamic Study of S-3304, a Novel Matrix Metalloproteinase Inhibitor, in Patients with Advanced and Refractory Solid Tumors
Authors: Alberto A. Chiappori, S. Gail Eckhardt, Ronald Bukowski, Daniel M. Sullivan, Minoru Ikeda, Yoshitaka Yano, Takuko Yamada-Sawada, Yoshikaze Kambayashi, Kazushige Tanaka, Milind M. Javle, Tarek Mekhail, Cindy L. O'Bryant, Patrick J. Creaven
Journal: Clinical Cancer Research (2007)

Abstract Purpose: Matrix metalloproteinases (MMP) play a fundamental role in cancer development and progression. S-3304 is a potent, orally active, noncytotoxic inhibitor of MMPs, primarily MMP-2 and MMP-9, that prolongs survival in mice xenografts and is well tolerated in healthy volunteers. Experimental Design: The aims of this phase I clinical trial were to determine the maximum tolerated dose, dose-limiting toxicities, pharmacokinetic profile, and intratumoral MMP inhibitory activity of single-agent S-3304 in advanced and refractory solid tumors. MMP activity was determined by film in situ zymography (FIZ). Patients had tumor biopsies before and after S-3304 administration and were also evaluated for response and survival. Results: Four dose levels were explored [DL1-DL4 or 800, 1,600, 2,400, and 3200 mg twice daily (BID), respectively], and 32 patients were enrolled. Toxicities were mostly gastrointestinal. The maximum tolerated dose was not reached, but dose escalations beyond DL4 were impractical (number of capsules needed). S-3304 steady-state concentrations were reached by day 8, and day 1 mean Cmax and AUC0-8 increases were less than dose proportional. After S-3304 administration, 17 of 18 patients experienced inhibition of MMP activity by FIZ. Strong mean inhibition of MMP activity was observed in DL1 to DL3. The negative mean inhibitory activity calculated for DL4 was due to one patient with a 397% MMP activity increase. Conclusion: S-3304 is safe, well tolerated, and achieves plasma concentrations above those required to inhibit MMP-2 and MMP-9. Its intratumoral MMP inhibitory activity has been shown using FIZ, which is useful as a biomarker with this and other MMP inhibitors.
Insertion/deletion polymorphism in the angiotensin-converting enzyme gene and risk of and prognosis after myocardial infarction
Authors: Nilesh J. Samani, Laurence O'Toole, Daniel Martin, Harjeet Rai, Sue Fletcher, David Lodwick, John R. Thompson, Alyn H. Morice, Kevin Channer, Kent L. Woods
Journal: Journal of the American College of Cardiology (1996)
Pathways and receptors involved in peptide YY induced contraction of rat proximal colonic muscle in vitro
Authors: L. Ferrier, J.P. Segain, P. Pacaud, Christine Cherbut, G. Loirand, J.P. Galmiche, Herve Blottiere
Journal: Gut (2000)

Peptide YY (PYY) is involved in the regulation of several gut functions, including secretion and motility. It exerts its effects through a family of six receptors, commonly named the Y receptor family.To characterise the effects of PYY on strips of rat proximal colon in vitro, and to determine the pathways and receptors involved.Contractions of strips removed from the muscle layer of rat proximal colon were recorded under isometric conditions, using PYY, Y receptor agonists and antagonists, and nerve blockers. Reverse transcription-polymerase chain reaction was also performed to detect the presence of mRNA coding for Y receptors. Finally, smooth muscle cells were isolated to estimate the cell length and intracellular Ca(2+) concentration in the presence and absence of PYY.PYY, neuropeptide Y (NPY), pancreatic polypeptide (PP) and [Leu31,Pro34]NPY induced a dose dependent contraction of strips from proximal colon. Tetrodotoxin partially inhibited the PYY and NPY induced contractions, and strongly inhibited the PP induced contraction. Specific antagonists showed the involvement of cholinergic nicotinic receptors and NK1 receptor. BIBP 3226, a specific Y1 antagonist, did not modify the colonic smooth muscle response to PYY, whereas blocking L-type Ca(2+) channels with D-600 abolished its effects. Moreover, PYY induced an increase in intracellular Ca(2+) concentration, associated with a reduction in cell length. mRNA encoding Y1 and Y4 receptors were detected in the muscle strips.These findings suggest that PYY stimulates colonic contractile activity in vitro through (a) a nervous Y4 dependent pathway and (b) a pathway involving a potential new receptor on myocytes.
Home phototherapy: report on a workshop of the British Photodermatology Group, December 1996
Authors: R.P.E. SARKANY, A. ANSTEY, B.L. DIFFEY, R. JOBLING, K. LANGMACK, J.M. MCGREGOR, H. MOSELEY, G.M. MURPHY, L.E. RHODES, P.G. NORRIS ON BEHALF OF THE BRITISH PHO
Journal: British Journal of Dermatology (1999)

Journal Article Home phototherapy: report on a workshop of the British Photodermatology Group, December 1996 Get access R.P.E. SARKANY, R.P.E. SARKANY Department of Dermatology, Addenbrooke's Hospital, Cambridge, CB2 2QQ, Search for other works by this author on: Oxford Academic Google Scholar A. ANSTEY, A. ANSTEY Department of Dermatology, Royal Gwent Hospital, Newport, Search for other works by this author on: Oxford Academic Google Scholar B.L. DIFFEY, B.L. DIFFEY Regional Medical Physics Department, Dryburn Hospital, Durham, Search for other works by this author on: Oxford Academic Google Scholar R. JOBLING, R. JOBLING St John's College, University of Cambridge, Cambridge, Search for other works by this author on: Oxford Academic Google Scholar K. LANGMACK, K. LANGMACK Department of Medical Physics, Addenbrooke's Hospital, Cambridge, Search for other works by this author on: Oxford Academic Google Scholar J.M. MCGREGOR, J.M. MCGREGOR Department of Photobiology, St John's Institute of Dermatology, London, Search for other works by this author on: Oxford Academic Google Scholar H. MOSELEY, H. MOSELEY Photobiology Unit, Department of Dermatology, Ninewells Hospital and Medical School, Dundee, U.K., Search for other works by this author on: Oxford Academic Google Scholar G.M. MURPHY, G.M. MURPHY Department of Dermatology, Beaumont Hospital, Dublin, Eire, Search for other works by this author on: Oxford Academic Google Scholar L.E. RHODES, L.E. RHODES Dermatology Unit, University Department of Medicine, Liverpool, U.K. Search for other works by this author on: Oxford Academic Google Scholar P.G. NORRIS ON BEHALF OF THE BRITISH PHOTODERMATOLOGY GROUP P.G. NORRIS ON BEHALF OF THE BRITISH PHOTODERMATOLOGY GROUP Department of Dermatology, Addenbrooke's Hospital, Cambridge, CB2 2QQ, Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 140, Issue 2, 1 February 1999, Pages 195–199, https://doi.org/10.1111/j.1365-2133.1999.02649.x Published: 01 February 1999
Mathematical Modeling of BTX: Biotransformation and Transport in the Subsurface
Authors: Linda M. Abriola, Yung-Ming Chen
Journal: Environmental Health Perspectives (1995)

A two-dimensional compositional model is presented; this model describes the transport and biotransformation of organic contaminants in a variably saturated subsurface environment. Modeled processes included mass exchange between constituent phases (water, air, soil, and organisms), advective and dispersive fluxes in the water phase, diffusive flux in the air phase, and biotransformation and biomass production in the biophase. In this model, solute transfer across air/water and water/solid interfaces is modeled using equilibrium relationships. Rate-limited mass transfer between the water and biophases is described with a linear driving force expression. Microbial degradation and biomass net growth are modeled by Monod-type kinetics. Solute transport and microbial growth equations are solved using an iterative Galerkin finite element method with a variable time-weighting scheme. Coupled biophase mass balance equations for each component are solved with a Newton-Raphson iterative scheme. Model capabilities are illustrated with two-dimensional, cross-sectional simulations of natural bioattenuation. The influence of biotransformation processes on the transport and extent of a toluene plume is examined.
PAINLESS INCISIONS BY INSTRUMENTS ADVANCING WITH A SLOW, IMPERCEPTIBLE MOTION.
Authors: EDMUND ANDREWS
Journal: JAMA (1884)

At a former meeting I called the attention of the Association to the painlessness of incisions and injuries when made by circular saws, bullets and other objects moving at a rate exceeding 200 feet in a second. I also detailed some experiments with a revolving knife made to move by a powerful spring at a similar velocity. A careful study of certain classes of surgical injuries, seems to show that pain exists only when the traumatic agent moves at a certain intermediate range of velocity, and that wounds made by objects moving on the one hand at a very high speed, or, on the other hand, at a very slow, imperceptible rate of motion, are nearly painless—often entirely so. Practical application of this law has long been made in surgery, where a fine rubber thread is made slowly and painlessly to cut through the sphincter in cases of fistula in
Bidirectional Glenn Procedure Improves the Mechanical Efficiency of a Total Cavopulmonary Connection in High-Risk Fontan Candidates
Authors: Yoshihisa Tanoue, Akira Sese, Yasutaka Ueno, Kunitaka Joh, Takayuki Hijii
Journal: Circulation (2001)

A total cavopulmonary connection (TCPC) is a widely performed surgical procedure for Fontan candidates. High-risk candidates who have undergone the bidirectional Glenn procedure (BDG) before TCPC have shown good results. The exact mechanism of this procedure, however, is still poorly understood. We hypothesized that a volume reduction with BDG improved ventricular contractility, thereby optimizing mechanical efficiency after TCPC.We measured percent normal systemic ventricular end-diastolic volume (%N-EDV), contractility (end-systolic elastance; E(es)), afterload (effective arterial elastance; E(a)), and mechanical efficiency (ventriculoarterial coupling; E(a)/E(es)) on the basis of the cardiac catheterization data before and after TCPC. Eighteen patients who underwent staged TCPC after BDG (staged group) were compared with 29 patients who underwent primary TCPC (primary group). E(es) and E(a) were approximated as follows: E(es)=mean arterial pressure/minimal ventricular volume, and E(a)=maximal ventricular pressure/(maximal ventricular volume-minimal ventricular volume), and E(a)/E(es) was then calculated. The ventricular volume was normalized with the body surface area. A canine experimental model with conductance catheter was used to validate the accuracy of this approximation of E(es) and E(a). %N-EDV decreased after TCPC in both groups. In the staged group, a smaller ventricular volume resulted in better contractility (E(es)). Although afterload (E(a)) increased in both groups, the increment of E(a) was smaller in the staged group. These changes resulted in an improvement of E(a)/E(es) in the staged group, whereas E(a)/E(es) increased in the primary group.The volume reduction of BDG preceding TCPC allows for any afterload mismatch to be corrected, thereby improving ventricular energetics after TCPC.
Modern Practical Neurology: An Introduction to Diagnosis and Management of Common Neurologic Disorders
Authors: Kurt A. Jaeckle
Journal: JAMA (1981)

This reasonably brief neurology textbook has a problem-oriented format with occasional topic-oriented chapters. The book is directed at "medical students, house officers, and physicians who undertake to manage patients with neurological disorders." The text can be read in a short time, which might make it useful for students on brief rotations or for those in other specialties who desire a lucid "core text" of neurology. It will not suffice as a major reference for neurologists, nor was it intended to. Chapters have the continuity associated with single-authored texts. Dr Scheinberg mentions his own anecdotal experience fairly infrequently, instead collating information from the major papers in the literature. References for each chapter are arranged categorically, but statements in the text proper are not cited individually. The chapter on the neurological examination is brief and should be read in conjunction with similar chapters in larger neurological texts. Cerebrovascular disease is covered nicely