tbuckley/cabot-search huggingface dataset:
Abstract 2320: N-cadherin down-regulation has antitumor effects in esophageal cancer
Authors: Seishi Nishitani, Kazuhiro Noma, Toshiaki ohara, shunsuke tanabe, yasuhiro fujiwara, Takayuki Motoki, Kazuhumi sakurama, Munenori Takaoka, Yasuhiro Shirakawa, Tomoki Yamatuji, Junji Matuoka, Yoshio Naomoto, Minoru Haisa
Journal: Cancer Research (2010)

Abstract Tumor microenviroment plays a critical role for cancer and their malignancy. Dynamic changes in tumor microenvironment have been observed in many tumors including esophageal cancer. And during the drastic change, some of tumor cells show EMT (epithelial mesenchymal transition) which means that epithelial cells lose their epithelial feature and acquire mesenchymal properties, as invasiveness and also communication with other kinds of mesenchymal cells. During those change, one of the marker of epithelial feature, E-cadherin is switch to N-cadherin, it has been known as “cadherin switch”. And it is thought that those changes have relations with cancer malignancy. Previously we reported that esophageal cancer cells secrete TGF-b1 and activate mesenchymal fibroblasts, and those activated fibroblasts guided more endothelial cells into tumor and induced angiogenesis. In the other hand, we hypothesis cell-cell direct communication like cell-cell contact is also important role for cancer progression. So in this report, firstly we analyze the expression of cadherins in surgical specimens in immunohistochemistry and determined expression patterns of N-cadherin in esophageal squamous cell carcinoma and Barrett's adenocarinoma. Some of those cancers showed N-cadherin expression and specifically expressed in their invasive front. Secondary we analyzed cancer cell lines as well, TE-1, TE-4, TE-10, OE19 and OE33. Those cell lines are squamous cell carcinoma cell lines and Barrett's adenocarcinoma cell lines, and those showed expression of E-cadherin and some of them showed expression of N-cadherin. And we used those cell lines and explored the behavioral differentiations of each cell lines. Here, we report and show analysis of E- or N- cadherin expression in surgical specimens and cancer cell lines. And also we could show the potential of regulation of cadherins in esophageal cancer as a new therapeutic target, which is well recognized as one of the most aggressive malignancies in the world. 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 2320.
Abstract 172: A role for the demethylation of microRNA-496 in MBD2-mediated repression
Authors: Sebastian G. Alvarado, Stephen D. Andrews, Flora Chik, Moshe Szyf
Journal: Cancer Research (2010)

Abstract BACKGROUND: MicroRNAs are small RNA molecules that have the ability to repress target mRNAs through binding in their 3’ UTR. Prior work has shown that the expression of methyl binding domain protein 2 (MBD2) induces a variety of prometastatic genes through direct demethylation. HYPOTHESIS: MBD2 turns on microRNA expression through promoter demethylation that in turn suppress other genes. RESULTS: Methylated DNA Immunoprecipitation (mDIP) and MBD2 ChIP arrays identified a subset of microRNAs that change with the overexpression and transient knockdown of MBD2 in MCF10A and MCF7 cell lines, respectively. Methylation of these microRNAs with bisulfite sequencing and validation of MBD2 binding with quantitative PCR (qPCR) revealed the possible induction of hsa-mir-496 by MBD2. Expression of mir-496 was shown to be induced in MBD2 transfected MCF10A cells and repressed in MCF7 and MDA-231 cells with qPCR. Luciferase promoter assays revealed hsa-mir-496 promoter to be regulated by methylation and driven forward by co-transfection with MBD2. In silico scans of possible targets of hsa-mir-496 identified CPEB3 as a putative target. Expression of CPEB3 was shown to be inversely proportional to MBD2 in MBD2 transfected MCF10A cell lines and transient knockdowns of MBD2 in MCF7 and MDA-231 cell lines with qPCR. CONCLUSIONS: The discovery of microRNAs has shed a whole new light on transcriptional regulation and with it has raised several questions about specific cell states. Considering that MBD2 causes complete transformation of a cell and plays a large role in tumorigenicity it is essential to characterize the roles of microRNA action with regards to MBD2 and its respective network of action. More importantly to show MBD2 as a key regulator of microRNA expression can further reinforce its role as a DNA demethylase and a key regulator of cancer. FUTURE DIRECTIONS: Future work will involve testing mir-496 action in the cell with its putative target CPEB3 using 2-O-methyl primer assays in conjunction with luciferase reporter assays in order to probe the functionality of the CPEB3 3′UTR. The aforementioned results and directions will give us a refined picture of our model as well as attempt to define a system of MBD2-microRNA action. 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 172.
Statistical approaches to the identification of late asthmatic reactions
Authors: SC Stenton, AJ Avery, EH Walters, DJ Hendrick
Journal: European Respiratory Journal (1994)

Late asthmatic reactions can be difficult to recognize because of their prolonged time course and the confounding effects of superimposed circadian rhythms of ventilatory function. Conventional methods of analysis are rather arbitrary. They depend for example on a 15 or 20% fall in forced expiratory volume in one second (FEV1) from baseline or from time-matched control measurements. We have, therefore, investigated whether statistical approaches applied to individual subjects can assist in the identification of late asthmatic reactions. In two separate series of aerosol inhalation tests, three symptomatic workers, three asthmatic controls and three nonasthmatic controls were challenged blindly with increasing doses of two chemical agents, and saline. One of the agents, sodium isononanoyl oxybenzene sulphonate (SINOS) was a suspected cause of occupational asthma. Prior to the challenges, FEV1 was measured hourly on three control days. Cumulative late changes on both control and active challenge days were quantified as the area between a line extrapolated from a 10.00 h baseline and the actual measurements from 12.00-22.00 h (the 2-12 h area decrement). The area decrement measurements on control and active challenge days were compared using Student's t-tests. The sensitivity of this method for detecting late asthmatic reactions among potentially positive tests (SINOS challenge tests in the workers) was examined, as was its specificity. The latter was determined from the false positive rate among the negative tests. A second statistical method based on the pooled standard deviation of serial (hourly) FEV1 measurements was investigated in the same way. In total, the data from 220 challenge and 30 control days were available for analysis.(ABSTRACT TRUNCATED AT 250 WORDS)
Harrison's Principles of Internal Medicine
Authors: John J. Massarelli
Journal: JAMA (1984)

The first modern textbook of internal medicine was Osler's<i>The Principles and Practice of Medicine</i>, published in 1892. This was made possible by the development of bacteriology in the last third of the 19th century, and the consequent assignment of specific causes to the illnesses most patients were initially seen with in those days. For the first time it was practical to have a nosography based on etiology. Osler's breadth of knowledge, clinical orientation, and mastery of English prose made the book a tremendous success. New editions appeared every two or three years. In 1927, an entirely new textbook of medicine came out, edited by Dr Russell Cecil, but written by 130 contributors. It soon replaced<i>Osler</i>(by then edited by McCrae) as the standard American medical text. Cecil retained Osler's format, with discrete descriptions of "disease entities" grouped by etiology or by systems affected. In 1950, another textbook was
EXPOSURE TO OXIDIZED LDL PROMOTES EPIGENETIC RE-PROGRAMMING RENDERING HUMAN ENDOTHELIAL CELLS RESISTANT TO LEUKOCYTE ADHESION
Authors: Sona Mitra, Magomed Khaidakov, Said Khaidakov, Srikanth Reddy Rasula, Jawahar L. Mehta
Journal: Journal of the American College of Cardiology (2011)
Atlas III: Illustrations of The Nervous System
Authors: Lyle M. Sellers
Journal: JAMA (1962)

This is an atlas of function and it is of great value to anyone interested in the basic neurological functions specific to a specialty. The diagrams are models of clarity, and they are definitive in the tracts presented. Here is that rarity of rarities—a practical, workable atlas of function. It is well composed, accurate so far as it goes, and of excellent format.
Capecitabine Plus Erlotinib in Gemcitabine-Refractory Advanced Pancreatic Cancer
Authors: Matthew H. Kulke, Lawrence S. Blaszkowsky, David P. Ryan, Jeffrey W. Clark, Jeffrey A. Meyerhardt, Andrew X. Zhu, Peter C. Enzinger, Eunice L. Kwak, Alona Muzikansky, Colleen Lawrence, Charles S. Fuchs
Journal: Journal of Clinical Oncology (2007)

The addition of either capecitabine or erlotinib to gemcitabine in the first-line treatment of advanced pancreatic cancer is associated with modest improvements in overall survival. We evaluated an oral regimen of capecitabine and erlotinib in patients with advanced pancreatic cancer who had experienced treatment failure with standard first-line therapy with gemcitabine.Thirty patients with gemcitabine-refractory metastatic pancreatic cancer were treated with capecitabine, administered at a dose of 1,000 mg/m2 twice daily for 2 weeks, followed by a 1-week break. All patients also received erlotinib 150 mg daily. Patients were observed for evidence of response, toxicity, and survival. EGFR mutational status was assessed in available tumor blocks.Treatment with capecitabine and erlotinib in gemcitabine-refractory patients was associated with an overall objective radiologic response rate of 10% and a median survival duration of 6.5 months. In addition, 17% of the treated patients experienced decreases in tumor marker (CA 19-9) levels of more than 50% from baseline. Common toxicities included diarrhea, skin rash, fatigue, and hand-foot syndrome. EGFR mutations were detected in two of five available tumors; no association between treatment response and EGFR mutational status was evident.The combination of capecitabine and erlotinib is active in patients with gemcitabine-refractory pancreatic cancer. This regimen may represent an acceptable treatment option in patients who experience treatment failure with standard first-line therapy with gemcitabine or for whom gemcitabine may not be an appropriate first-line treatment option.
Anaesthesia by acupuncture.
Authors: M A Ramsay
Journal: BMJ (1973)

long stay wards and hospitals.We fail to use the most effective therapeutic weapons we have-civilized and interesting conditions in which to live and meaningful things to do.We cannot plead a poverty-stricken society but like to think in terms of irresponsible families.There is no evidence ot irresponsible families.3 4We cannot really face the issue of deterrence.The workhouse setup appeared to work in the past only be- cause of the compulsion of the Poor Law, and to expect it to work on a voluntary basis in an affluent society at the end of the 20th century is ludicrous.What Drs.Hodkinson and Jefferys do not appear to recognize is that the "social dehiscence" which they try so hard to avoid, but are not very clear about, has nearly always occurred already.It is the commonest single reason that brings people to hospital.It is a gaping, a bursting open, and not a withering.The metaphor is crucial because on it hangs the validity of their paper.We have two geriatric units side by side in very similar areas but using very differ- ent methods.There is no way of finding out from present statistics what happens to people who pass through hospital except in a very general way.
Alcohol intake and early-onset basal cell carcinoma in a case-control study
Authors: Y. Zhang, L.M. Ferrucci, B. Cartmel, A.M. Molinaro, D.J. Leffell, A.E. Bale, S.T. Mayne
Journal: British Journal of Dermatology (2014)

Previous epidemiological studies of overall alcohol intake and basal cell carcinoma (BCC) are inconsistent, with some evidence for differences by type of alcoholic beverage. While alcohol may enhance the carcinogenicity of ultraviolet (UV) radiation, this has not been evaluated in existing epidemiological studies.To evaluate alcohol intake in relation to early-onset BCC, and explore potential interactions with UV exposure.Basal cell carcinoma cases (n = 380) and controls with benign skin conditions (n = 390) under 40 years of age were identified through Yale Dermatopathology. Participants provided information on lifetime alcohol intake, including type of beverage, during an in-person interview. Self-reported data on indoor tanning and outdoor sunbathing were used to categorize UV exposure. We calculated odds ratios (OR) and 95% confidence intervals (CIs) using unconditional multivariate logistic regression in the full sample and in women only.There was no statistically significant association between lifetime alcohol intake and early-onset BCC overall [above median intake vs. no regular alcohol intake (OR 1·10, 95% CI 0·69-1·73)] or in women only (OR 1·21, 95% CI 0·73-2·01). Similarly, intake of red wine, white wine, beer or spirits and mixed drinks was not associated with early-onset BCC. In exploratory analyses, we saw limited evidence for an interaction (P(interaction) = 0·003), with highest risk for high alcohol and high UV exposures, especially in women, but subgroup risk estimates had wide and overlapping CIs.Overall, we did not observe any clear association between lifetime alcohol intake and early-onset BCC.
Clinical Equivalence of Generic and Brand-Name Drugs Used in Cardiovascular Disease
Authors: Aaron S Kesselheim, Alexander S Misono, Joy L Lee, Margaret R Stedman, M Alan Brookhart, Niteesh K Choudhry, William H Shrank
Journal: JAMA (2008)

<h3>Context</h3>Use of generic drugs, which are bioequivalent to brand-name drugs, can help contain prescription drug spending. However, there is concern among patients and physicians that brand-name drugs may be clinically superior to generic drugs.<h3>Objectives</h3>To summarize clinical evidence comparing generic and brand-name drugs used in cardiovascular disease and to assess the perspectives of editorialists on this issue.<h3>Data Sources</h3>Systematic searches of peer-reviewed publications in MEDLINE, EMBASE, and International Pharmaceutical Abstracts from January 1984 to August 2008.<h3>Study Selection</h3>Studies compared generic and brand-name cardiovascular drugs using clinical efficacy and safety end points. We separately identified editorials addressing generic substitution.<h3>Data Extraction</h3>We extracted variables related to the study design, setting, participants, clinical end points, and funding. Methodological quality of the trials was assessed by Jadad and Newcastle-Ottawa scores, and a meta-analysis was performed to determine an aggregate effect size. For editorials, we categorized authors' positions on generic substitution as negative, positive, or neutral.<h3>Results</h3>We identified 47 articles covering 9 subclasses of cardiovascular medications, of which 38 (81%) were randomized controlled trials (RCTs). Clinical equivalence was noted in 7 of 7 RCTs (100%) of β-blockers, 10 of 11 RCTs (91%) of diuretics, 5 of 7 RCTs (71%) of calcium channel blockers, 3 of 3 RCTs (100%) of antiplatelet agents, 2 of 2 RCTs (100%) of statins, 1 of 1 RCT (100%) of angiotensin-converting enzyme inhibitors, and 1 of 1 RCT (100%) of α-blockers. Among narrow therapeutic index drugs, clinical equivalence was reported in 1 of 1 RCT (100%) of class 1 antiarrhythmic agents and 5 of 5 RCTs (100%) of warfarin. Aggregate effect size (n = 837) was −0.03 (95% confidence interval, −0.15 to 0.08), indicating no evidence of superiority of brand-name to generic drugs. Among 43 editorials, 23 (53%) expressed a negative view of generic drug substitution.<h3>Conclusions</h3>Whereas evidence does not support the notion that brand-name drugs used in cardiovascular disease are superior to generic drugs, a substantial number of editorials counsel against the interchangeability of generic drugs.
Galen: [A Bibliographical Demonstration in the Library of the Faculty of Physicians and Surgeons of Glasgow, December 9th, 1891.]
Authors: J. Finlayson
Journal: BMJ (1892)

DICAL JOURL 77 in the various sections are treated.The language is clear, the illustrations are good, and the references are very satisfactory.The work is admirably suited for the dresser or practitioner on matters relating to minor surgery, wounds, hip disease, emergencies, and other subjects likely to come under his notice.The appendix contains a useful formulary.Yellow Fever.
Ionic currents in single smooth muscle cells of the canine renal artery.
Authors: C H Gelband, J R Hume
Journal: Circulation Research (1992)

Membrane currents from single smooth muscle cells enzymatically isolated from canine renal artery were recorded using the patch-clamp technique in the whole-cell and cell-attached configurations. These cells exhibited a mean resting potential, input resistance, membrane time constant, and cell capacitance of -51.8 +/- 2.1 mV, 5.2 +/- 0.98 G omega, 116.2 +/- 16.4 msec, and 29.1 +/- 2.0 pF, respectively. Inward current, when elicited from a holding potential of -80 mV, activated near -50 mV, reached a maximum near 0 mV and was sensitive to the dihydropyridine agonist Bay K 8644 and dihydropyridine antagonist nisoldipine. Two components of macroscopic outward current were identified from voltage-step and ramp depolarizations. The predominant charge carrier of the net outward current was identified as K+ by tail-current experiments (reversal potential, -61.0 +/- 0.8 mV in 10.8 mM [K+]o 0 mM [K+]i). The first component was a small, low-noise, voltage- and time-dependent current that activated between -40 and -30 mV (IK(dr)), and the second component was a larger, noisier, voltage- and time-dependent current that activated at potentials positive to +10 mV (IK(Ca)). Both IK(dr) and IK(Ca) displayed little inactivation during long (4-second) voltage steps. IK(Ca) and IK(dr) could be pharmacologically separated by using various Ca2+ and K+ channel blockers. IK(Ca) was substantially inhibited by external NiCl2 (500 microM), CdCl2 (300 microM), EGTA (5 mM), tetraethylammonium (Ki at +60 mV, 307 microM), and charybdotoxin (100 nM) but was insensitive to 4-aminopyridine (0.1-10 mM). IK(dr) was inhibited by 4-aminopyridine (Ki at +10 mV, 723 microM) and tetraethylammonium (Ki at +10 mV, 908 microM) but was insensitive to external NiCl2 (500 microM), CdCl2 (300 microM), EGTA (5 mM), and charybdotoxin (100 nM). Two types of single K+ channels were identified in cell-attached patches. The most abundant K+ channel that was recorded exhibited voltage-dependent activation, was blocked by external tetraethylammonium (250 microM), and had a large single-channel conductance (232 +/- 12 pS with 150 mM K+ in the patch pipette, 130 +/- 17 pS with 5.4 mM K+ in the patch pipette). The second channel was also voltage dependent, was blocked by 4-aminopyridine (5 mM), and exhibited a smaller single-channel conductance (104 +/- 8 pS with 150 mM K+ in the patch pipette, 57 +/- 6 pS with 5.4 mM K+ in the patch pipette). These results suggest that depolarization of canine renal artery cells opens dihydropyridine-sensitive Ca2+ channels and at least two K+ channels.(ABSTRACT TRUNCATED AT 400 WORDS)
Remarks on a Case of Bright's Disease, Attended with Cardiac Thrombosis and Haemorrhagic Infarctions of the Spleen, Left Kidney, and Lungs
Authors: J. B. Bradbury
Journal: BMJ (1872)

THE BRITISH MEDICAL 7OURNAL.37 as a sedative, but aids the radical cure of the disease, inasmuch as it causes the subsequently administered ferruginous preparations to be borne more easily.Both general and local blood-lettings may be used; but the blood must be taken in small quantities, a couple of ounces at a time being quite sufficient."In such a case, you slhould diminish or omit the iron for a time and use morphia or bromide of potassium, with chloral, or valerian, or stimulants in small quantities.Instead of seeking to increase the quan- tity of the menstrual discharge, you will rather aim at diminishing it; particularly in cases where it keeps up in quantity whilst the patient is becoming more and more chlorotic.This diminution we may effect by keeping the patient in bed or on a couch for a couple of days before menstruation begins, and also whilst it is in progress ; giving, at the csame time, some bromide of potassium till the period is half over, and then using extract of ergot.Digitalis in some cases checks the flow, and this may be used instead of ergot when this drug seems to have no effect.
Megakaryocytes constitute a functional component of a plasma cell niche in the bone marrow
Authors: Oliver Winter, Katrin Moser, Elodie Mohr, Dimitra Zotos, Henriette Kaminski, Martin Szyska, Katrin Roth, David M. Wong, Christof Dame, David M. Tarlinton, Harald Schulze, Ian C. M. MacLennan, Rudolf A. Manz
Journal: Blood (2010)
Predictability of the Response to the Ergonovine Test
Authors: Joseph L. Gerry, Stephen C. Achuff, Lewis C. Becker, Malcolm S. Pond, H. Leon Greene
Journal: JAMA (1979)

Thirty-five patients with atypical chest pain were given ergonovine maleate as a provocative test for coronary spasm. None of the patients had significant coronary atherosclerosis. The patients were divided into two groups based on clinical information available before ergonovine testing. Group 1 patients (n=13) had objective evidence of cardiac disease manifested by episodes of syncope, ventricular tachyarrhythmias, myocardial infarction, or transient ST segment shifts with chest pain. Group 2 patients had chest pain but no objective evidence of cardiac disease. The ergonovine test was positive in 11 of 13 patients in group 1. None of the 22 group 2 patients had a positive response to ergonovine. These data suggest that ergonovine testing does not allow for any more precise recognition of patients with atypical chest pain who have coronary artery spasm than do clinical data alone.
The Changing Congressional Process
Authors: John S. Zapp
Journal: JAMA (1986)

During recent years, perhaps the most important factors affecting the ability of an organization, such as the American Medical Association (AMA), to influence the outcome of legislation has been the increasing complexity of and change in the process by which the Congress makes law. Over the years, those of us who deal with Congress have come to rely on certain fundamental procedures that guide and control the lawmaking process. These procedures are important not only from the standpoint of bringing some order to the business of lawmaking, but also because they serve to ensure that Congress does not operate in a vacuum isolated from public input. The congressional process provides benchmarks for those of us who have a responsibility for affecting the legislative outcome. From these benchmarks, we develop strategies for achieving a favorable result. When the process changes to the extent that it has in the past few years,