tbuckley/cabot-search huggingface dataset:
Meningioma Transcript Profiles Reveal Deregulated Notch Signaling Pathway
Authors: Ileana C. Cuevas, Alison L. Slocum, Peter Jun, Joseph F. Costello, Andrew W. Bollen, Gregory J. Riggins, Michael W. McDermott, Anita Lal
Journal: Cancer Research (2005)

Abstract Meningiomas constitute the second most common central nervous system tumor, and yet relatively little is known about the molecular events that are important for the pathogenesis and malignant progression of these tumors. We have used serial analysis of gene expression to compare the transcriptomes of nonneoplastic meninges and meningiomas of all malignancy grades. A novel finding from this screen is the induction of three components of the Notch signaling pathway: the transcription factor, hairy and enhancer of Split1 (HES1) and two members of the Groucho/transducin-like enhancer of Split family of corepressors, TLE2 and TLE3. TLE corepressors interact and modulate the activity of a wide range of transcriptional regulatory systems, one of which is HES1. We have shown that the transcript and protein levels of HES1, the Notch2 and Notch1 receptors and the Jagged1 ligand are induced in meningiomas of all grades, whereas induction of TLE2 and TLE3 occurs specifically in higher-grade meningiomas. Meningioma cell lines express components of the Notch signaling pathway and an inhibitor of this pathway suppresses meningioma cell survival. These results suggest that deregulated expression of the Notch pathway is a critical event in meningioma pathogenesis and that modulation of this and potentially other signaling pathways by TLE corepressors leads to a more malignant phenotype.
Genomic and Epigenomic Integration Identifies a Prognostic Signature in Colon Cancer
Authors: Joo Mi Yi, Mashaal Dhir, Leander Van Neste, Stephanie R. Downing, Jana Jeschke, Sabine C. Glöckner, Marilia de Freitas Calmon, Craig M. Hooker, Juan M. Funes, Chris Boshoff, Kim M. Smits, Manon van Engeland, Matty P. Weijenberg, Christine A. Iacobuzio-Donahue, James G. Herman, Kornel E. Schuebel, Stephen B. Baylin, Nita Ahuja
Journal: Clinical Cancer Research (2011)

Abstract Purpose: The importance of genetic and epigenetic alterations maybe in their aggregate role in altering core pathways in tumorigenesis. Experimental Design: Merging genome-wide genomic and epigenomic alterations, we identify key genes and pathways altered in colorectal cancers (CRC). DNA methylation analysis was tested for predicting survival in CRC patients using Cox proportional hazard model. Results: We identified 29 low frequency-mutated genes that are also inactivated by epigenetic mechanisms in CRC. Pathway analysis showed the extracellular matrix (ECM) remodeling pathway is silenced in CRC. Six ECM pathway genes were tested for their prognostic potential in large CRC cohorts (n = 777). DNA methylation of IGFBP3 and EVL predicted for poor survival (IGFBP3: HR = 2.58, 95% CI: 1.37–4.87, P = 0.004; EVL: HR = 2.48, 95% CI: 1.07–5.74, P = 0.034) and simultaneous methylation of multiple genes predicted significantly worse survival (HR = 8.61, 95% CI: 2.16–34.36, P &amp;lt; 0.001 for methylation of IGFBP3, EVL, CD109, and FLNC). DNA methylation of IGFBP3 and EVL was validated as a prognostic marker in an independent contemporary-matched cohort (IGFBP3 HR = 2.06, 95% CI: 1.04–4.09, P = 0.038; EVL HR = 2.23, 95% CI: 1.00–5.0, P = 0.05) and EVL DNA methylation remained significant in a secondary historical validation cohort (HR = 1.41, 95% CI: 1.05–1.89, P = 0.022). Moreover, DNA methylation of selected ECM genes helps to stratify the high-risk stage 2 colon cancers patients who would benefit from adjuvant chemotherapy (HR: 5.85, 95% CI: 2.03–16.83, P = 0.001 for simultaneous methylation of IGFBP3, EVL, and CD109). Conclusions: CRC that have silenced genes in ECM pathway components show worse survival suggesting that our finding provides novel prognostic biomarkers for CRC and reflects the high importance of integrative analyses linking genetic and epigenetic abnormalities with pathway disruption in cancer. Clin Cancer Res; 17(6); 1535–45. ©2011 AACR.
EUS training in a live pig model: does it improve echo endoscope hands-on and trainee competence?
Authors: M. Barthet, M. Gasmi, C. Boustiere, M. Giovannini, J. Grimaud, S. Berdah
Journal: Endoscopy (2007)

The learning curve for endoscopic ultrasonography (EUS) is known to be difficult, especially in the field of pancreatic and biliary diseases. The aim of this study was to assess the impact of a live pig model developed for EUS credentialing in France.A total of 17 trainees obtained hands-on EUS experience using a live pig model. Trainees were asked to visualize anatomical structures, to carry out fine-needle aspiration (FNA) on lymph nodes in the liver hilum, and to perform celiac neurolysis. Assessment of the FNA procedure or celiac neurolysis included measurement of time (seconds), evaluation of the precision of the puncture (mm), and existence of technical errors.A significant improvement between a pre-test and post-test was observed for diagnostic procedures in the following anatomical areas: splenic mesenteric vein, vena cava, splenic mesenteric artery, celiac tree, pancreatic gland, and bile duct. For lymph node FNA, a significant improvement was observed in the duration of the procedure (84 seconds vs. 60 seconds; P = 0.01), and precision (4.2 mm vs. 1.8 mm; P = 0.009), but not for the rate of technical error (29% vs. 6%; not significant [n. s.]). For celiac neurolysis, a significant improvement was observed in procedure time (150 seconds vs. 84 seconds; P = 0.003), but not in the rate of technical error (6% vs. 6%; n. s.) or precision (4.2 mm vs. 2.8 mm; n. s.).Teaching EUS with a live pig model significantly increased competence in diagnostic procedures with regard to visualizing anatomical structures, performance of FNA and, to a lesser extent, EUS-guided celiac neurolysis.
Helicobacter pylori Infection in Intestinal- and Diffuse-Type Gastric Adenocarcinomas
Authors: J. Parsonnet, D. Vandersteen, J. Goates, R. K. Sibley, J. Pritikin, Y. Chang
Journal: JNCI Journal of the National Cancer Institute (1991)

Gastric cancer can be divided into two histologic types: intestinal and diffuse. To determine whether Helicobacter pylori , a bacterium linked with gastritis, was associated with either cancer type, we reviewed histologic sections from stomachs of patients who had undergone gastrectomy for gastric cancer. Of 37 of the sections with evidence of intestinal-type cancer, 33 (89.2%) contained H pylori in noncancerous tissue compared with 7 (31.8%) of 22 of the sections with evidence of diffuse-type cancer (odds ratio = 17.7; P .001). This association remained strong when controlled for age, sex, site, and number of sections reviewed. The prevalence of H pylori in intestinal-type gastric cancer far exceeded the prevalence of H pylori in diffuse disease and that described in the normal US population. This finding suggests that H pylori may be a cofactor in development of intestinal-type gastric cancer. [J Nati Cancer Inst 83:640–643, 1991]
Myeloperoxidase produces nitrating oxidants in vivo
Authors: Joseph P. Gaut, Jaeman Byun, Hung D. Tran, Wendy M. Lauber, James A. Carroll, Richard S. Hotchkiss, Abderrazzaq Belaaouaj, Jay W. Heinecke
Journal: Journal of Clinical Investigation (2002)

Despite intense interest in pathways that generate reactive nitrogen species, the physiologically relevant mechanisms for inflammatory tissue injury remain poorly understood. One possible mediator is myeloperoxidase, a major constituent of neutrophils, monocytes, and some populations of macrophages. The enzyme uses hydrogen peroxide and nitrite to generate 3-nitrotyrosine in vitro. To determine whether myeloperoxidase produces nitrating intermediates in vivo, we used isotope dilution gas chromatography/mass spectrometry to quantify 3-nitrotyrosine in two models of peritoneal inflammation: mice infected with Klebsiella pneumoniae and mice subjected to cecal ligation and puncture. Both models developed an intense neutrophil inflammatory response, and the inflammatory fluid contained markedly elevated levels of 3-chlorotyrosine, a marker of myeloperoxidase action. In striking contrast, 3-nitrotyrosine levels rose only in the mice infected with K. pneumoniae. Levels of total nitrite and nitrate were 20-fold higher in mice injected with K. pneumoniae than in mice subjected to cecal ligation and puncture. Levels of 3-nitrotyrosine failed to increase in mice infected with K. pneumoniae that lacked functional myeloperoxidase. Our observations provide strong evidence that myeloperoxidase generates reactive nitrogen species in vivo and that it operates in this fashion only when nitrite and nitrate become available.
Commentary: practicalities of seeking consent and gaining understanding
Authors: R. Gill
Journal: BMJ (2010)

Farrell and Brazier set out the arguments for obtaining specific informed consent for allogeneic blood transfusion.1 They do not deal with allogeneic blood products, but I think their article can be assumed to cover this too. This subject is controversial, and the question of how to seek and record consent has been the subject of a recent consultation by the Department of Health’s Advisory Committee on the Safety of Blood, Tissues and Organs. A question Farrell and Brazier avoid is who should be responsible for gaining informed consent? Should it be those who provide the blood (the transfusion service, probably most informed about the risks) or those who prescribe it (probably least informed)? This is of crucial importance in the debate and has considerable …
Bahrain is accused of incarcerating doctors in secret and without charge
Authors: S. Arie
Journal: BMJ (2011)

Authorities in Bahrain are systematically arresting and “disappearing” doctors and nurses in an ongoing campaign to prevent medical professionals from treating people injured in pro-democracy protests, a new report says.

At least 32 medical workers have been arrested since street protests began in the small Gulf state in February, states the report, published on 22 April by the US based group Physicians for Human Rights.

Several doctors have been arrested and not heard from since, says the report. The surgeon Ali El-Ekri was taken from the operating room while he was performing surgery at Salmaniya …
Maxwell &amp;amp; Kleeman's Clinical Disorders of Fluid and Electrolyte Metabolism
Authors: James Stim
Journal: JAMA (1994)

The fifth edition of Maxwell & Kleeman's Clinical Disorders of Fluid and Electrolyte Metabolism continues as the most comprehensive and authoritative textbook devoted to a subject of such importance. It consists of 49 well-written chapters whose 115 contributors include many leading authorities in their fields.  The contents are split between part 1, encompassing the normal physiological basis for water and electrolyte metabolism, and part 2, dealing with the clinical syndromes of disordered fluid and electrolyte metabolism. The book opens with a chapter covering the basic physiology of body water compartmentation, with an emphasis on methodology of total body water and compartmentation measurements. Next is a section on epithelial transport, which concisely reviews molecular models of membrane transport, membrane transporting proteins, physical forces that affect membrane transport of ions, and integration of mechanisms that coordinate transmembrane transport. The remainder of part 1 covers monovalent and divalent cations, phosphorus, water, and acid-base
The Diagnostic Value of the Forced Expiratory Time-Reply
Authors: Ralph M. Schapira
Journal: JAMA (1994)

In Reply.  —We thank Drs Kern and Patel for their thoughts as to why the FET as a diagnostic test of OAD proved better in our study than theirs. 1 Kern and Patel state that a limitation of our study was that the population was limited to preoperative subjects. We performed a cross-sectional, blinded study to evaluate the PET using a group of 400 consecutive subjects who presented to the pulmonary-function testing laboratory of a large hospital. Our subject population was representative of a clinic population using the services of a tertiary care hospital. In contrast, the study by Kern and Patel was limited to 229 plumbers who volunteered to participate in a screening examination for asbestos-related disease. The markedly different results probably reflect differences in study populations. In our population, we found a 55% prevalence of OAD. For diagnostic purposes, a FET threshold of 6 seconds or greater provides
THE IMPACT OF PARAOXONASE 1 ACTIVITY ON THE INCIDENCE OF INTRA STENT THROMBUS AFTER DRUG ELUTING STENT IMPLANTATION IN THE JAPANESE CYP2C19 LOSS OF FUNCTION POLYMORPHISM CARRIERS
Authors: Ryo Nishio, Toshiro Shinke, Hiromasa Otake, Junya Shite, Ken-ichi Hirata
Journal: Journal of the American College of Cardiology (2012)
Undiagnosed diseases are focus of new NIH programme
Authors: Bob Roehr
Journal: BMJ (2008)

Patients who have confounded doctors with signs and symptoms that elude diagnosis are to be offered the expertise of hundreds of doctors in a unique programme from the US National Institutes of Health."Physicians deal with about 6600 conditions and 6000 of them are quite rare.Even common diseases have many subtypes," the institutes' director Elias A Zerhouni said during a telephone news conference with reporters earlier this week.He said it was not surprising that many can go undiagnosed for years.The programme aims to combine the revolution in tools and information at the molecular level with the expertise of the 1600 doctors at the NIH Clinical Center "to assist patients around the country and their doctors."It will add to the knowledge base by creating a phenotype atlas of disease."We are doing this now because of the advances that have been made over the last five years at the fundamental level.We have many more biologic markers, the significance of which is not always understood." Dr Zerhouni said that for the first time his organisation was going to apply these sophisticated laboratory tests to human diseases on a large scale.Under the current system of research at the NIH Clinical Center, patients with challenging conditions "are triaged to a specific institute or protocol programme, and are assessed by one team," said John I Gallin, director of the centre.Participants in the new programme "will be assessed by a large spectrum of teams."Candidate patients must be referred by a healthcare provider and will have to submit exhaustive medical records that will be reviewed by a multidisciplinary team of 25 senior doctors.Those who are accepted into the programme will travel to the centre for an evaluation, which is likely to take at least a week.Details are available at http://rarediseases.info.nih.gov/
Detection of Recurrent Renal Cell Carcinoma by Three-Phase Bone Scan
Authors: DENNIS W. WULFECK, NOLAN K. SAKOW, SEYTHAN SENLER
Journal: Clinical Nuclear Medicine (1993)

The use of three-phase bone imaging in patients with low back pain has been questioned. This case demonstrates the usefulness of the three-phase bone scan in patients with a known malignancy presenting with low back pain.
Reduced dose of lenograstim is as efficacious as standard dose of filgrastim for peripheral blood stem cell mobilization and transplantation: A randomized study in patients undergoing autologous peripheral stem cell transplantation
Authors: Selmin Ataergin, Fikret Arpaci, Mustafa Turan, Luis Solchaga, Turker Cetin, Mustafa Ozturk, Ahmet Ozet, Seref Komurcu, Bekir Ozturk
Journal: American Journal of Hematology (2008)

In vitro studies have demonstrated a 27% increased efficacy of lenograstim over filgrastim. However, equal doses of 10 microg/kg/day of filgrastim and lenograstim have been recommended for mobilization of CD34+ cells without associated chemotherapy. In this study, we investigated whether a 25% reduced dose of lenograstim at 7.5 microg/kg/day is equavalent to 10 microg/kg/day filgrastim for autologous peripheral blood stem cell (PBSC) mobilization and transplantation. A total of 40 consecutive patients were randomized to either filgrastim (n = 20) or lenograstim (n = 20). The two cohorts were similar in regard to disease, sex, body weight, body surface area, conditioning regimens, previous chemotherapy cycles and radiotherapy. Each growth factor was administered for 4 consecutive days. The first PBSC apheresis was done on the 5th day. In the posttransplant period, the same G-CSF was given at 5 microg/kg/day until leukocyte engraftment. Successful mobilization was achieved in 95% of patients. Successful mobilization with the first apheresis, was achieved in 10/20 (50%) patients in the filgrastim group versus 9/20 (46%) patients in the lenograstim group. No significant difference was seen in the median number of CD34+cells mobilized, as well as the median number of apheresis, median volume of apheresis, percentage of CD34+ cells, and CD34+ cell number. Leukocyte and platelet engraftments, the number of days requiring G-CSF and parenteral antibiotics, the number of transfusions were similar in both groups in the posttransplant period. Lenograstim 7.5 microg/kg/day is as efficious as filgrastim 10 microg/kg/day for autologous PBSC mobilization and transplantation.
Gene transfer of CD40-ligand induces autologous immune recognition of chronic lymphocytic leukemia B cells.
Authors: K Kato, M J Cantwell, S Sharma, T J Kipps
Journal: Journal of Clinical Investigation (1998)

CD40-CD40-ligand (CD154) interactions play a critical role in immune activation. Using replication defective adenovirus encoding mouse CD154 (Ad-CD154), we modified human chronic lymphocytic leukemia B cells to express a functional ligand for CD40. This not only induces expression of immune accessory molecules on the infected cell, but also allows it to trans-activate noninfected bystander leukemia B cells. Also, factors that impair the antigen-presenting capacity of leukemia B cells are downmodulated. Ad-CD154- infected leukemia cells are highly effective stimulators in mixed lymphocyte reactions and can induce generation of cytotoxic T lymphocytes specific for autologous nonmodified leukemia cells. As such, Ad-CD154 can induce a host antileukemia response that may have therapeutic potential.
FDG PET Imaging of Signet-Ring Cell Adenocarcinoma of the Stomach
Authors: Mark K. Buyyounouski, William J. Klump, Andre Konski, Hong Wu, Lee P. Adler
Journal: Clinical Nuclear Medicine (2005)

A 40-year-old man experiencing early satiety, a 25-lb weight loss, and intermittent nausea underwent an esophagogastroduodenoscopy, which demonstrated an ulcerated mass of the stomach extending from 43 cm to 53 cm from the incisors occupying the gastroesophageal junction, gastric cardia, fundus, and body. A biopsy of the gastric body showed diffuse infiltration of the lamina propria by poorly differentiated signet-ring cell adenocarcinoma. F-18 fluorodeoxyglucose (FDG) positron emission tomography (PET) with computed tomography demonstrated minimally increased FDG uptake relative to normal tissues. Further study to determine the use of FDG PET in the evaluation of patients with gastric signet-ring cell carcinoma is warranted.
Resuscitating Wild-Type p53 Expression by Disrupting Ceramide Glycosylation: A Novel Approach to Target Mutant p53 Tumors
Authors: Yong-Yu Liu
Journal: Cancer Research (2011)

Mutant p53 is frequently detected in cancers in which p53 has lost its ability in tumor suppression and gained function in promoting tumor progression. Restoration of p53 functions by replacement of wild-type p53 and inhibition of its degradation or increment of its transcriptional activity has been applied to the prevention and treatment of cancers. Recent evidence indicates that disrupting ceramide glycosylation can resuscitate wild-type p53 expression and p53-dependent apoptosis in mutant p53 tumors. A posttranscriptional process that can turn on wild-type p53 expression and abrogate mutant p53 may provide a new strategy to eradicate mutant p53 cancers.
Improved Detection of Early Iron Deficiency
Authors: John B. Chessare
Journal: JAMA (1985)

<h3>To the Editor.—</h3> In a recent article inThe Journal, McClure et al<sup>1</sup>reported an improved method—red blood cell distribution width—for the detection of early iron deficiency in nonanemic subjects; however, their methodology for determining iron deficiency, namely, serum transferrin saturation, and their statement that reduced iron saturation equates with chemical evidence of iron deficiency must be challenged. The gold standard for the diagnosis of iron deficiency is the absence of stainable iron stores in the bone marrow. An acceptable and more easily attainable alternative method is measurement of the serum ferritin level. A serum ferritin level less than 12 μg/L is diagnostic of iron deficiency.<sup>2</sup>Normal serum ferritin levels in the presence of deficient bone marrow iron stores have been reported in rheumatoid arthritis, hepatic disease, leukemia, lymphoma, and active inflammatory bowel disease; however, exclusion of these diseases is relatively simple and, thus, the serum ferritin level
US Physicians in International Health
Authors: Morris M. Weiss
Journal: JAMA (1984)

To the Editor.—  A recent article inThe Journaldiscussed the role of US physicians in international medicine. 1 We report another dimension open to American physicians interested in promoting communication between our peers in other countries.  A team of ten physicians from the Jewish Hospital in Louisville, a private, nonprofit, university-affiliated community hospital, recently traveled to Lima, Peru, to take part in an International Medical Congress. All travel costs incurred during this trip were borne by the physicians. Logistic support and administrative costs were provided by the Jewish Hospital.  These physicians, representing a range of medical and surgical subspecialties, presented papers and made ward rounds at government Social Security hospitals. The impetus for this venture began with a Peruvian orthopedic surgeon trained in our Hand Service.  An important result of this trip has been an agreement signed between the Peruvian Social Security Institute and Jewish Hospital providing for the
Prescribing Ready-made Compounds.
Authors: W. T. Akins
Journal: JAMA (1898)

Chicago, Feb. 9, 1898. <h3>To the Editor:</h3> —In the prevention and successful treatment of disease our science culminates and becomes an art. Therapeutics, the philosophic adaptation of remedial agents to the correction of pathologic conditions, the cure of disease in the human organism and its restoration to that physiologic equipoise we dominate health, is the full consummation of science and art. No one unfamiliar with physiology and pathology, pharmaco dynamics and therapeutics can prescribe for any disease in a scientific manner. Therapeutics must be regarded as first among the principles of scientific medicine by learned and cultured members of our profession. The adaptation of means to the accomplishment of wisely purposed ends in the practice of medicine and surgery, implies much as to acquirements and knowledge? Every case is stamped with an individuality by which it is differentiated from all others. We find special perversions of functions and pathologic tendencies
The Female World
Authors: Natalie Shainess
Journal: JAMA (1981)

This large and closely written book calls to mind another, half the size but also weighty: Elizabeth Janeway's<i>Powers of the Weak</i>. Both are full of information, and yet unsatisfactory. They are like smorgasbords from which we may sample many tidbits, but leave without the feeling of having eaten a good solid meal, perhaps suffering indigestion at the same time. The lack of consistent development of a central theme is the problem, even though the title cogently offers one. Bernard's premise is certainly correct: that we all live in a "singlesex world,"—men in their world, women in theirs, these worlds interconnecting—and that most of what we know historically and socially deals with the<i>male</i>world. This is certainly applicable to medicine, although there were some notable women healers in the past. Unfortunately, Bernard does not attempt to include this information. Her effort to describe the "group structure" of the female