tbuckley/cabot-search huggingface dataset:
Abstract 2056: MicroRNA-126 inhibits SOX2 expression in gastric cancer cells
Authors: Takeshi Otsubo, Yoshimitsu Akiyama, Yutaka Hashimoto, Yasuhito Yuasa
Journal: Cancer Research (2010)

Abstract A transcription factor SOX2 is essential for embryonic development and play critical roles in the maintenance of embryonic stem cell's pluripotency. We previously reported that SOX2 plays important roles in growth inhibition through cell cycle arrest and apoptosis, and SOX2 expression was frequently down-regulated in gastric cancers, some of which were due to aberrant DNA methylation. However, the mechanisms underlying loss of SOX2 expression and its target genes involved in gastric carcinogenesis remain largely unknown. In this study, we initially assessed whether microRNAs, small noncoding RNAs, control SOX2 expression in gastric cancers. In silico analysis revealed that microRNA-126 (miR-126) has two predictive target sites in the 3′-UTR of the SOX2 mRNA. Gain- and loss-of function experiments demonstrated that miR-126 inhibited SOX2 expression in gastric cancer cell lines. Luciferase reporter assays with a pGL4-SOX2 3′-UTR vector revealed that miR-126 directly inhibits SOX2 expression by targeting two binding sites in the 3′-UTR of the SOX2 mRNA independently. Some primary gastric cancer tissues with low expression of SOX2 exhibited markedly high levels of miR-126 expression compared with paired non-cancerous mucosae. To further understand the potential effects of miR-126-induced down-regulation of SOX2 on gastric carcinogenesis, we next attempted to identify the downstream target genes of SOX2 in gastric cancer cells. The microarray analysis after SOX2 over-expression in a gastric cancer cell line showed that 437 genes were up-regulated (&amp;gt;2-fold) and 447 genes were down-regulated (&amp;lt;0.5-fold), some of which were cancer-related genes. Taken together, we identified miR-126 as a novel microRNA which inhibits SOX2 expression in gastric cancer cells, and suggest that aberrant miR-126 expression and consequent SOX2 down-regulation may contribute to gastric carcinogenesis. 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 2056.
Vitamin D state of Asians living in Pakistan.
Authors: A Rashid, T Mohammed, W P Stephens, S Warrington, J L Berry, E B Mawer
Journal: BMJ (1983)

Asians living in Pakistan have serum 25-hydroxycholecalciferol concentrations which are well within the normal range and significantly higher than in Asians resident in Britain. Clearly, Asians can maintain an adequate vitamin D state given an abundant supply of ultraviolet light, and the expression of vitamin D deficiency is an environmental and not a genetically determined characteristic. The risk of an Asian developing vitamin D deficiency increases after migration to Britain. The most efficient way to treat this is by supplementation with vitamin D.
1101-44 Effect of everolimus-eluting stents in preventing neointimal hyperplasia: An intravascular ultrasound analysis from the FUTURE II trial
Authors: Shinjo Sonoda, Eberhard Grube, Yoshihisa Shimada, Ali H.M Hassan, Yasuhiro Honda, Paul G Yock, Charles Chan, Hidehiko Honda, Saibal Kar, Karl E Hauptmann, Hans Storger, Alexandra J Lansky, Peter J Fitzgerald
Journal: Journal of the American College of Cardiology (2004)
A New Alpha in Line Between KRAS and NF-κB Activation?
Authors: Chorom Pak, Shigeki Miyamoto
Journal: Cancer Discovery (2013)

Abstract Summary: Bang and colleagues report a novel role for GSK-3α, rather than the well-studied GSK-3β, as the link between oncogenic KRAS and the canonical and noncanonical activation pathways of NF-κB in pancreatic cancer. Although the mechanism through which it promotes noncanonical activation remains unclear, the authors show that GSK-3α binds and stabilizes TAK1-TAB complexes to constitutively activate canonical NF-κB signaling. Consequently, the inhibition of GSK-3α retards pancreatic cancer growth in vitro and in vivo, thereby revealing this relatively less-studied kinase as a potential therapeutic target for treatment of KRAS-positive pancreatic cancer. Cancer Discov; 3(6); 613–5. ©2013 AACR. See related article by Bang et al., p. 690
ON THE ORIGIN AND TREATMENT OF CHRONIC DISEASES OF THE SKIN
Authors: T. Hunt
Journal: BMJ (1855)

Gs.zm.L Taz.rxzx.Akeratime.Next in efficiency to arseic may be mentioned the "iok of potaeitn.This mdicine, although it eerts its most potent influence on the perosteum, has also a specific, though a limited influ- ence, on the dermi.It has been found useful in squa- mous nd tubercular diseass, especially in lepra and lupus non-exedens; and its energy is considerably in- peased, if some mild form of mercurial, such as Plummer's pill, is administered with it.And here I may mention the triple compound known by the name of Donovan's solution, which consists of a chemical compound of iodine, mercury, and asenic.It will occasionally succeed when all its ele- ments, uncombined, fail.It is, however, a dangerous medi- * The rond on which the ointment was recommended, was that no medine haed given, eacapt prv&es, in a ase wohid it cured on 23 July
Dimensions of modelling: Generality and integrativeness
Authors: Jeffrey C. Schank
Journal: Behavioral and Brain Sciences (2001)

Webb has articulated a clear, multi-dimensional framework for discussing simulation models and modelling strategies. This framework will likely co-evolve with modelling. As such, it will be important to continue to clarify these dimensions and perhaps add to them. I discuss the dimension of generality and suggest that a dimension of integrativeness may also be needed.
The Right Road for Medicine-Reply
Authors: John J. Ring
Journal: JAMA (1992)

<h3>In Reply.</h3> —Dr Kibelstis raises an important point concerning cost shifting and the relationships among access to health care, payment for health services, and possession of health care insurance. Access to health care is a complex issue involving the availability of a physician, the willingness of the physician to treat the patient, and the affordability of needed hospital services, drugs, and laboratory tests, which are related to the medical service provided by the physician. To a patient, high out-of-pocket expenses or the high cost of health insurance may make access limited or, in some circumstances, unavailable. Physicians should be allowed to charge their patients a fair fee. As professionals, however, they must also be sensitive to the needs of their patients. Physicians should provide adequate fee information prior to the provision of service and should consider reduced fees where appropriate. Professionalism and fairness also call for physicians to cooperate
Activation of KATP channels suppresses glucose production in humans
Authors: Preeti Kishore, Laura Boucai, Kehao Zhang, Weijie Li, Sudha Koppaka, Sylvia Kehlenbrink, Anna Schiwek, Yonah B. Esterson, Deeksha Mehta, Samar Bursheh, Ya Su, Roger Gutierrez-Juarez, Radhika Muzumdar, Gary J. Schwartz, Meredith Hawkins
Journal: Journal of Clinical Investigation (2011)

Increased endogenous glucose production (EGP) is a hallmark of type 2 diabetes mellitus. While there is evidence for central regulation of EGP by activation of hypothalamic ATP-sensitive potassium (K(ATP)) channels in rodents, whether these central pathways contribute to regulation of EGP in humans remains to be determined. Here we present evidence for central nervous system regulation of EGP in humans that is consistent with complementary rodent studies. Oral administration of the K(ATP) channel activator diazoxide under fixed hormonal conditions substantially decreased EGP in nondiabetic humans and Sprague Dawley rats. In rats, comparable doses of oral diazoxide attained appreciable concentrations in the cerebrospinal fluid, and the effects of oral diazoxide were abolished by i.c.v. administration of the K(ATP) channel blocker glibenclamide. These results suggest that activation of hypothalamic K(ATP) channels may be an important regulator of EGP in humans and that this pathway could be a target for treatment of hyperglycemia in type 2 diabetes mellitus.
Endoscopic Orientation within the Duodenal Bulb
Authors: R. J. Straker, J. C. Bienvenu, H. J. Nord
Journal: Endoscopy (1992)

Laparotomy performed for bleeding duodenal ulcer after diagnostic/therapeutic endoscopy revealed a disparity in location of the lesion on several occasions at our institution. The position of the duodenal lesion is important in assessing bleeding potential. Twenty consecutive patients underwent upper gastrointestinal endoscopy by a staff and trainee gastroenterologist to evaluate the ability to determine the true posterior position of the duodenal bulb. Documentation of the posterior bulb location was verified by pooled colored fluid with the patient in a supine position. True posterior location was chosen only 30% of the time by an experienced gastroenterologist. This observation may have clinical implications in assessing the patient's bleeding potential and in the use of coaptive coagulation for control of ulcer bleeding.
Impaired endothelium-dependent relaxation to aggregating platelets and related vasoactive substances in porcine coronary arteries in hypercholesterolemia and atherosclerosis.
Authors: H Shimokawa, P M Vanhoutte
Journal: Circulation Research (1989)

Vasoconstrictor responses are augmented in porcine coronary arteries in hypercholesterolemia and atherosclerosis, leading to an occurrence of coronary vasospasm in the latter condition. The role of the endothelium in the vascular hyperreactivity in hypercholesterolemic and atherosclerotic coronary arteries was examined, particularly in response to aggregating and related vasoactive substances. Male Yorkshire pigs underwent balloon endothelial denudation of the left anterior descending coronary artery (LAD) and 2% high-cholesterol feeding for 10 weeks. Electron microscopic examination demonstrated a full lining of endothelial cells in the LAD and the left circumflex coronary artery (LCX). Endothelium-dependent responses were examined in vitro. In cholesterol-fed animals, endothelium-dependent relaxations to aggregating platelets, serotonin, ADP, bradykinin, thrombin, and the calcium ionophore A23187 were depressed in LAD (atherosclerosis), while the relaxations to aggregating platelets, serotonin and ADP were depressed in LCX (hypercholesterolemia). Serotonin-induced contractions were endothelium-dependently augmented in atherosclerotic LAD; the endothelium-dependent component of the contractions was inhibited by blockers of cyclooxygenase. Bioassay studies demonstrated a depressed release of endothelium-derived relaxing factor(s) from the atherosclerotic LAD in response to serotonin. These experiments indicate that the endothelium-dependent relaxations to aggregating platelets and related vasoactive substances are severely impaired in atherosclerosis and moderately impaired in hypercholesterolemia. Since coronary atherosclerosis was induced by a combination of balloon endothelial injury (and regeneration) and high-cholesterol feeding in this study, the combined effects of those factors must account for the severely impaired responses in atherosclerosis. The depressed release of the endothelium-derived relaxing factor(s) and the concomitant release of vasoconstrictor product(s) of cyclooxygenase appear to be responsible for the impaired relaxations.
Suppression of in vitro monoclonal human rheumatoid factor synthesis by antiidiotypic antibody. Target cells and molecular requirements.
Authors: W J Koopman, R E Schrohenloher, J C Barton, E C Greenleaf
Journal: Journal of Clinical Investigation (1983)

Previous studies have indicated that antiidiotypic antibody can modulate expression of idiotype both in vivo and in vitro. Although the precise mechanisms underlying modulation of idiotype expression by antiidiotype remains unclear, a requirement for intact IgG antiidiotypic antibody has been suggested and T cells appear to play a role in some systems. We have studied peripheral blood mononuclear leukocytes (MNL) from a patient with a B cell lymphoma and a circulating IgMK rheumatoid factor (RF) paraprotein in an effort to delineate mechanisms involved in regulation of idiotype expression by antiidiotypic antibody. 1-10% of MNL from this patient could be cytoplasmically stained with specific F(ab')2 antiidiotypic antibody. MNL from the patient spontaneously synthesized IgM RF in culture that possessed the same idiotype as the circulating IgM RF paraprotein. Production of RF by MNL was suppressed by pretreatment with either intact IgG or the F(ab')2 fragments of antiidiotypic antibody (50% inhibitory concentration was 0.2 and 1.1 micrograms/culture, respectively). In contrast, the Fab' fragment of antiidiotypic antibody was not inhibitory (up to 57 micrograms/culture) despite retaining demonstrable antiidiotype activity. Suppression of RF production was not observed over the same concentration range with the IgG or F(ab')2 fractions of a non-cross-reactive antiidiotypic antibody prepared against another monoclonal IgMK RF paraprotein or with IgG or F(ab')2 fractions prepared from normal rabbit serum. Inhibition of RF production by antiidiotypic antibody did not require T cells. Antiidiotypic antibody decreased intracellular and extracellular levels of idiotype indicating diminished synthesis of idiotype by the patient's B cells. Synthesis of IgM RF by MNL obtained from unrelated donors was not suppressed by the antiidiotypic antibody specific for the patient's paraprotein. The results indicate that (a) antiidiotypic antibody is capable of directly suppressing human B cell release of idiotype, (b) the bivalent antigen-binding fragment (F[ab']2) of antiidiotypic antibody is sufficient for mediating such suppression, (c) an intact Fc portion of antiidiotypic antibody enhances suppression of idiotype, and (d) antiidiotypic antibody inhibits idiotype expression by suppressing synthesis of idiotype.
Thresholds for food allergens and their value to different stakeholders
Authors: R. W. R Crevel, B. K. Ballmer‐Weber, T. Holzhauser, J. O’B. Hourihane, A. C. Knulst, A. R. Mackie, F. Timmermans, S. L. Taylor
Journal: Allergy (2008)

Thresholds constitute a critical piece of information in assessing the risk from allergenic foods at both the individual and population levels. Knowledge of the minimum dose that can elicit a reaction is of great interest to all food allergy stakeholders. For allergic individuals and health professionals, individual threshold data can inform allergy management. Population thresholds can help both the food industry and regulatory authorities assess the public health risk and design appropriate food safety objectives to guide risk management. Considerable experience has been gained with the double‐blind placebo‐controlled food challenge (DBPCFC), but only recently has the technique been adapted to provide data on thresholds. Available data thus vary greatly in quality, with relatively few studies providing the best quality individual data, using the low‐dose DBPCFC. Such high quality individual data also form the foundation for population thresholds, but these also require, in addition to an adequate sample size, a good characterization of the tested population in relation to the whole allergic population. Determination of thresholds at both an individual level and at a population level is influenced by many factors. This review describes a low‐dose challenge protocol developed as part of the European Community‐funded Integrated Project Europrevall, and strongly recommends its wider use so that data are generated that can readily increase the power of existing studies.
Inappropriate Drug Prescribing-Reply
Authors: David U. Himmelstein
Journal: JAMA (1995)

<h3>In Reply.</h3> —Like some correspondents, we have prescribed from our list of contraindicated drugs, sometimes appropriately. Why refuse a dying patient's request for propoxyphene? But in reviewing our own charts we found far more instances of ill-considered prescribing of inappropriate drugs. Discussions with full-time practitioner colleagues at our department meetings assured us that our deficiencies were not unique. Subsequently, in our hospital, use of the contraindicated drugs in elderly inpatients fell by two thirds without regulatory intervention. Perhaps this collegial interchange was more successful than our article in conveying our goal of improving care, not blaming physicians. We are troubled by the defensive tone of some letters. There is a raft of evidence that physicians often prescribe poorly. Our article surely understates the frequency; we didn't assess good drugs used for bad indications, at excessive doses, for too long, or with interacting agents. If<i>JAMA</i>isn't an appropriate forum to
Points: Are spinal injuries more common in rugby union than rugby league football?
Authors: D. A D Macleod
Journal: BMJ (1984)

and Dr R Wise (21 April, p 1179) emphasised the toll exacted by pneumococcal infections but did not make it clear that pneu- mococcal bacteraemia generally occurs in people with pre-existing disease.In a study of 103 cases of pneumococcal bacteraemia at East Birmingham Hospital pre-existing disease was found in 820' of the 79 patients aged over 20 and in 38 of the 41 aged between 40 and 70.1 Most of the underlying diseases involved the respiratory system, major metabolic processes, or the immune system.In the latter group the most common disorder was hyposplenism.
Effects of the faecal stream and stasis on the ileal pouch mucosa.
Authors: H J de Silva, P R Millard, N Soper, M Kettlewell, N Mortensen, D P Jewell
Journal: Gut (1991)

This study aimed to investigate the effects of the faecal stream and stasis on the mucosa of ileal pouches. Nine patients were followed up. Two pouch biopsy specimens were obtained from each at the time of pouch formation, ileostomy closure, and three, six, and 12 months after operation. None developed pouchitis. Two pouch biopsy specimens each were also obtained from 20 patients (six with pouchitis), whose pouches had been functioning for at least a year and in whom pouch evacuation was assessed by radioisotope labelled artificial stool. Biopsy specimens were assessed for the degree of acute and chronic inflammation, mucin type (high iron diamine-alcian blue stain), a morphometric index of villous atrophy (villous height:total mucosal thickness), and crypt cell proliferation (using the monoclonal antibody Ki67). Mean values from the two biopsy specimens were obtained for each parameter. After three months of pouch function, the scores for acute and chronic inflammation, the degree of sulphomucin, and crypt cell proliferation were significantly higher, and the index of villous atrophy was significantly lower (indicating a greater degree of villous atrophy), than at pouch formation or at ileostomy closure. The values at pouch formation and ileostomy closure were similar. For all parameters, the changes seen at six and 12 months were not significantly different from those at three months. There was no significant correlation between the efficiency of pouch evacuation and any of the mucosal changes. It is concluded that exposure to the faecal stream is necessary for changes to take place in the pouch mucosa, although the amount of stasis, as measured by radioisotopic evacuation studies, seems to be irrelevant. The mucosal changes occur soon after ileostomy closure and then remain stable for at least one year.
The Evaluation of an Ultrasonic Flow Detector for the Assessment of Peripheral Vascular Disease
Authors: J. S. Allan, H. J. Terry
Journal: Cardiovascular Research (1969)

The circulation in the lower limbs of 50 patients with vascular disease was assessed transcutaneously with a commercially available ultrasonic flow detector. In 66 limbs, the results were compared with arteriograms. The findings were entirely correct in 57 limbs, and in every limb a reliable indication of the adequacy of the blood supply was obtained.
364 PERCUTANEOUS ACETIC ACID INJECTION VERSUS PERCUTANEOUS ETHANOL INJECTION FOR SMALL HEPATOCELLULAR CARCINOMA: A LONG-TERM FOLLOW UP STUDY
Authors: J.S. Cheng, W.L. Tsai, G.H. Lo, K.H. Lai, P.I. Hsu, W.L. Li
Journal: Journal of Hepatology (2008)
Analysis of Ventricular Dimension in the Unanesthetized Dog
Authors: ISHIO NINOMIYA, MICHAEL F. WILSON, John M. Gibson, Richard H. Segnitz
Journal: Circulation Research (1965)

Left ventricular dynamics was studied in the unanesthetized dog by an analysis of simultaneous recordings of left ventricular transverse dimension, pressure, and ascending aortic flow in 16 experiments while the dogs were reclining, standing, and during graded treadmill exercise. Statistical analysis of the dimension data revealed typical patterns of isovolumetric changes which suggest asynchronous contraction and relaxation. The fact that maximum and minimum dimension levels did not coincide with levels at onset and end of ejection led to the concept of the "effective" stroke shortening in the left ventricular transverse dimension. An ellipsoid of revolution was the best approximation of left ventricular shape while reclining and standing, but during exercise the shape constant decreased toward a paraboloid of revolution. Analysis of the data from correlation coefficients and by using the principle of the compression ratio, which is independent of shape, indicated that stroke shortening and stroke volume may be a function of initial length or volume for the resting states but that during exercise their increase was due primarily to extrinsic influences which acted to change the magnitude of the contractile response.
Communication difficulties during 999 ambulance calls: observational study
Authors: J Higgins, S Wilson, P Bridge, M W Cooke
Journal: BMJ (2001)

One of the key roles of ambulance call receivers is to obtain accurate information concerning the location of the patient and their complaint.The automatic tracing of calls to their source can accurately determine the location of most patients.Obtaining information on the patient's condition, however, depends on effective communication between the call maker and the call receiver.Ambulance services in the United Kingdom now use priority dispatch systems to categorise calls according to the level of urgency for medical treatment and to provide first aid advice (for example, cardiopulmonary resuscitation). 1 2 The safety and effectiveness of priority dispatch has been assessed 3 ; however, whether call receivers are able to procure accurate and reliable information has not been established.This study aimed to determine the nature and extent of communication problems encountered during 999 calls.
Value and Limitations of Continuous-Wave Doppler Echocardiography in Estimating Severity of Valvular Stenosis
Authors: Mikel D. Smith
Journal: JAMA (1986)

DOPPLER echocardiography is a valuable new technique that provides a noninvasive method of detecting both direction and velocity of intracardiac blood flow. Perhaps the single most important use of Doppler echocardiography today is in the quantitation of valvular stenosis. Clinical clues and traditional noninvasive tests such as phonocardiography and echocardiography are quite useful for the detection of aortic and mitral stenosis, yet have been shown to have serious limitations in the quantitation of such lesions. 1,2 Doppler echocardiography provides physiologic information concerning flow across an orifice and allows for the estimation and location of pressure gradients. Nevertheless, application of Doppler for this purpose requires considerable expertise, and care must be taken to avoid common pitfalls in performance and interpretation of the Doppler examination. The purpose of this article is to explain the technical basis of Doppler echocardiography, to examine its role in estimating pressure gradients, and to point out some