tbuckley/cabot-search huggingface dataset:
Abstract 3951: EphA10 exhibits anti-apoptotic activity through its dominant-negative role for EphA signaling in cancer cells
Authors: Shuji Sato, Hiroshi Tanaka, Yuichi Hikichi, Eiji Sunahara, Isao Kaieda, Takafumi Ishii, Koji Yoshimura
Journal: Cancer Research (2010)

Abstract Eph receptors are members of receptor tyrosine kinase family. They are activated by binding of their ligands, ephrins, which regulate numerous physiological responses, including axon guidance, and pattern formation during development. In addition to their important roles during development, several members of the Eph receptor family have been reported to function in carcinogenesis. Recently EphA10 was isolated as the 16th member of the Eph receptor family. EphA10 is expressed in normal testis and binds to ephrin-A. However, biological functions of EphA10 remain unclear. We demonstrate here that EphA10 functions as a dominant-negative receptor for EphA signaling. Our results show that EphA10 is over-expressed in cancer tissues, especially breast and lung cancer tissues as compared with patient-matched adjacent normal tissues. EphA10 binds to ephrin-A2, 3, 4, and 5. Analysis of the amino acid sequence of EphA10 revealed that EphA10 does not have Lys and Asp in the kinase domain, which are necessary for kinase activity nor two Tyr in the juxtamembrane domain, which are necessary for phosphorylation. As expected from the amino acid sequence, no intrinsic tyrosine kinase activity of EphA10 was detected despite its interaction with ephrin-A. To further investigate the mechanism of EphA10 signaling, we tested the role of EphA10 in modulating ephrin-A4 activity. In our experiment, ephrin-A4 suppressed phosphorylation of ERK1/2 in HEK293 cells. EphA10 over-expression in HEK293 cells reduced the effect of ephrin-A4 on ERK1/2. Conversely, reduction of EphA10 expression by antisense oligonucleotides induced apoptosis in the breast cancer cell line ZR-75-1. In addition to its role in shunting ephrin-A response through binding to ephrin-A directly, we found that EphA10 formed a hetero-complex with functional EphA7, suggesting that EphA10 may block EphA signaling by forming non-functional hetero complexes with other functional EphA receptors. Our studies demonstrated that EphA10 has anti-apoptotic function in cancer cells by blocking EphA signaling through its dominant-negative activity. Thus, EphA10 potentially plays an important role in cancer cell survival. 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 3951.
Subepithelial Fibrosis and Degradation of the Bronchial Extracellular Matrix in Cystic Fibrosis
Authors: ISABELLE DURIEU, SIMONE PEYROL, DOMINIQUE GINDRE, GABRIEL BELLON, DENIS VITAL DURAND, YVES PACHECO
Journal: American Journal of Respiratory and Critical Care Medicine (1998)

Cystic fibrosis is a genetic disease caused by mutations of the cystic fibrosis transmembrane conductance regulator gene. Chronic inflammation and proteolysis lead to progressive damage of the bronchial wall. Extracellular matrix determines the structural organization and the mechanical properties of lung airways. It was thus examined in nine patients with cystic fibrosis (six bronchial biopsies and three lobectomies) in order to assess its level of alteration. The submucosal changes in matrix protein distribution were analyzed by immunochemistry and electron microscopy: the subepithelial basal lamina was thinned; an acellular collagen fiber layer composed of interstitial collagens (types I and III) subtended by tenascin and devoid of elastin-associated microfibrils was deposited beneath the basal lamina; this dense fibrous deposit generally formed a thick layer and could extend into the bronchial wall; the bronchial elastic framework lost arborescent distribution and appeared slender, packed, or lacunar; ultrastructural observation gave evidence for elastic and collagenic fiber lysis. Proteolytic activity is probably the major cause of matrix degradation. Fibrosis appears as a repair process rather than as an active fibrogenesis. The reversibility of extracellular matrix alterations is an important challenge and various interventions such as anti-inflammatory treatments can be targeted to halt or reverse this degradation process.
Predictors of Family Risk for Celiac Disease: A Population-Based Study
Authors: Alberto Rubio–Tapia, Carol T. Van Dyke, Brian D. Lahr, Alan R. Zinsmeister, Mounif El–Youssef, S. Breanndan Moore, Martha Bowman, Lawrence J. Burgart, L. Joseph Melton, Joseph A. Murray
Journal: Clinical Gastroenterology and Hepatology (2008)
Imitation and the effort of learning
Authors: Justin H. G. Williams
Journal: Behavioral and Brain Sciences (2008)

Abstract Central to Hurley's argument is the position that imitation is “automatic” and requires inhibition. The evidence for this is poor. Imitation is intentional, involves active comparison between self and other, and involves new learning to improve self-other likeness. Abnormal imitation behaviour may result from impaired learning rather than disinhibition. Mentalizing may be similarly effortful and dependent upon learning about others.
Pooled Analysis of Elderly Patients with Non-small Cell Lung Cancer Treated with Front Line Docetaxel/Gemcitabine Regimen: The Hellenic Oncology Research Group Experience
Authors: Athanasios G. Pallis, Aris Polyzos, Ioannis Boukovinas, Athina Agelidou, Lambros Lamvakas, Xanthi Tsiafaki, Maria Agelidou, Georgia Pavlakou, Vassilis Chandrinos, Stelios Kakolyris, Charalambos Christophyllakis, Nikolaos Kentepozidis, Stelios Giassas, Nikolaos Androulakis, Sophia Agelaki, Vassilis Georgoulias
Journal: Journal of Thoracic Oncology (2008)
Intracerebral hemorrhage, cerebral infarction, and subdural hematoma after acute myocardial infarction and thrombolytic therapy in the Thrombolysis in Myocardial Infarction Study. Thrombolysis in Myocardial Infarction, Phase II, pilot and clinical trial.
Authors: J M Gore, M Sloan, T R Price, A M Randall, E Bovill, D Collen, S Forman, G L Knatterud, G Sopko, M L Terrin
Journal: Circulation (1991)

In the Thrombolysis in Myocardial Infarction, Phase II pilot and clinical trial, 908 patients [326 (35.9%) in the pilot study and 582 (64.0%) in the randomized study] were treated with 150 mg recombinant tissue-type plasminogen (rt-PA) activator in combination with heparin and aspirin, and 3,016 patients [64 (2.1%) in the pilot study and 2,952 (97.9%) in the randomized study] were treated with 100 mg rt-PA in combination with heparin and aspirin. Adverse neurological events occurred in 23 patients treated with 150 mg rt-PA (2.5%) [nine cerebral infarctions (1.0%), 12 intracerebral hemorrhages (1.3%), and two subdural hematomas (0.2%)] and in 33 patients treated with 100 mg rt-PA (1.1%) [20 cerebral infarctions (0.7%), 11 intracerebral hemorrhages (0.4%), and two subdural hematomas (0.1%)]. The difference in adverse neurological events observed comparing the two rt-PA regimens was primarily due to a higher frequency of intracerebral bleeding among patients treated with 150 mg rt-PA (1.3% versus 0.4%, p less than 0.01). Patients with recent (within 6 months) histories of stroke were not eligible for the study, and patients with any history of cerebrovascular disease were declared ineligible early in the study. The small number of patients (89, or 2.3%) with any history of neurological disease, intermittent cerebral ischemic attacks, or stroke who were enrolled before the stricter eligibility criteria were imposed or on the basis of incomplete baseline information experienced an increased frequency of intracerebral hemorrhage compared with patients without such histories (3.4% versus 0.5%). Mortality at 6 weeks after presentation among 23 patients who had intracerebral hemorrhage was 47.8%. Intracerebral hemorrhage is a severe but infrequent complication of rt-PA therapy for acute myocardial infarction. The combined frequency of intracerebral hemorrhage, subdural hematoma, and cerebral infarction after treatment with 100 mg rt-PA is comparable to that observed in other trials with thrombolytic agents in acute myocardial infarction.
Rubiazol in Nose and Throat Conditions
Authors: E. Carew-Shaw
Journal: BMJ (1939)

of wrong material or by faulty technique allowing introduction of septic infection.It is but right to point out that no such accident has been proved in this country, and to emphasize that the process of immunization is one which can be guaranteed as not only thoroughly safe and harmless but reliable in providing protection against diphtheria in the vast majority of those inoculated.Furthermore, its application to young children at the earliest age, preferably during or soon after the first year of life, is to be urged, in order to ensure freedom from attack at the most susceptible period before reaching school age, and thus to secure the necessary protection during inevitable exposure to infection in school years.
A feed-forward spinal cord glycinergic neural circuit gates mechanical allodynia
Authors: Yan Lu, Hailong Dong, Yandong Gao, Yuanyuan Gong, Yingna Ren, Nan Gu, Shudi Zhou, Nan Xia, Yan-Yan Sun, Ru-Rong Ji, Lize Xiong
Journal: Journal of Clinical Investigation (2013)

Neuropathic pain is characterized by mechanical allodynia induced by low-threshold myelinated Aβ-fiber activation. The original gate theory of pain proposes that inhibitory interneurons in the lamina II of the spinal dorsal horn (DH) act as "gate control" units for preventing the interaction between innocuous and nociceptive signals. However, our understanding of the neuronal circuits underlying pain signaling and modulation in the spinal DH is incomplete. Using a rat model, we have shown that the convergence of glycinergic inhibitory and excitatory Aβ-fiber inputs onto PKCγ+ neurons in the superficial DH forms a feed-forward inhibitory circuit that prevents Aβ input from activating the nociceptive pathway. This feed-forward inhibition was suppressed following peripheral nerve injury or glycine blockage, leading to inappropriate induction of action potential outputs in the nociceptive pathway by Aβ-fiber stimulation. Furthermore, spinal blockage of glycinergic synaptic transmission in vivo induced marked mechanical allodynia. Our findings identify a glycinergic feed-forward inhibitory circuit that functions as a gate control to separate the innocuous mechanoreceptive pathway and the nociceptive pathway in the spinal DH. Disruption of this glycinergic inhibitory circuit after peripheral nerve injury has the potential to elicit mechanical allodynia, a cardinal symptom of neuropathic pain.
Patients with ERCC1-Negative Locally Advanced Esophageal Cancers May Benefit from Preoperative Chemoradiotherapy
Authors: Min Kyoung Kim, Kyung-Ja Cho, Gui Young Kwon, Seung-Il Park, Yong Hee Kim, Jong Hoon Kim, Ho-Young Song, Ji Hoon Shin, Hwoon Yong Jung, Gin Hyug Lee, Kee Don Choi, Sung-Bae Kim
Journal: Clinical Cancer Research (2008)

Abstract Purpose: To assess the significance of excision repair cross-complementation group 1 (ERCC1) expression as a predictive marker, we analyzed the effects of preoperative chemoradiotherapy on survival relative to ERCC1 status in patients with locally advanced operable esophageal cancer. Experimental Design: Paraffin-embedded pretreatment tumor specimens, collected by endoscopic biopsy from patients treated with surgery alone or with preoperative chemoradiotherapy followed by surgery, were immunohistochemically assayed for ERCC1 expression. Results: Of the 175 patients, 152 biopsy specimens were available for immunohistochemical analysis. Based on a median ERCC1 expression score of 1, we divided the samples into ERCC1-positive (score &amp;gt;1; 71 patients, 47%) and ERCC1-negative (score ≤1; 81 patients, 53%) groups. No differences in patient and disease characteristics were observed between the two groups. However, among patients with ERCC1-negative tumors, those who received preoperative chemoradiotherapy had longer overall survival (OS) and event-free survival (EFS) than those treated with esophagectomy alone (median OS, 59.2 versus 25.4 months, P = 0.057; median EFS, 50.7 versus 19.7 months, P = 0.042). This difference was not observed among patients with ERCC1-positive tumors. In multivariate analysis, treatment modality was the major determinant of both EFS (P = 0.006) and OS (P = 0.008) for patients with ERCC1-negative tumors, whereas Eastern Cooperative Oncology Group performance status was the only significant predictor of outcome among ERCC1-positive patients. Among patients who received esophagectomy alone, those with ERCC1-positive tumors had a tendency toward longer OS and EFS (P = 0.085 and 0.094, respectively). Conclusions: Patients with ERCC1-negative operable esophageal tumors show a greater benefit from preoperative chemoradiotherapy followed by esophagectomy than those who undergo esophagectomy alone.
Ectopic gastric mucosa in the rectum mimicking an early depressed cancer treated by endoscopic mucosal resection
Authors: H. Ikematsu, K. Fu, Y. Saito, T. Matsuda, T. Shimoda, T. Fujii
Journal: Endoscopy (2007)

A 69-year-old man visited our hospital due to a positive fecal occult blood test. He was asymptomatic and his medical history included myocardial infarction and hypertension. At colonoscopy, a depressed lesion, approximately 7 mm in size, was identified in the posterior wall of the lower part of the rectum. Chromoendoscopy with 0.4 % indigo carmine defined the depression, which mimicked an early depressed cancer. However, magnified observation after 0.05 % crystal violet staining demonstrated a type I-like pit pattern according to Kudo’s classification in the depressed area ([Figure 1]) [1]. Therefore, this lesion was diagnosed as non-neoplastic based on the pit pattern analysis. An endoscopic biopsy provided a histological diagnosis of ectopic gastric mucosa of the fundic type. Although the lesion exhibited no change in size or morphology after 1 year of follow-up, it was completely removed by endoscopic mucosal resection (EMR) for both diagnostic and therapeutic reasons. Histological examination of the resected specimen revealed fundic-type gastric mucosa surrounded by normal rectal mucosa; Helicobacter pylori was not detected in the resected specimen ([Figure 2]).
DENGUE IN THE ISTHMIAN CANAL ZONE.INCLUDING A REPORT ON THE LABORATORY FINDINGS.
Authors: DUDLEY NEWCOMB CARPENTER
Journal: JAMA (1905)

Of the several tropical diseases whose etiology is yet in question, dengue undoubtedly stands at the head of the list in importance. It has long been considered an infectious disease, as the writings of Ornstein,<sup>1</sup>Eulenberg,<sup>2</sup>Graham<sup>3</sup>and Hirsch<sup>4</sup>attest, while we find Leichenstein,<sup>5</sup>Malie,<sup>6</sup>von Duringe<sup>7</sup>and a half dozen others presenting almost indisputable evidence that it is contagious, in the technical sense of the word, as well. McLaughlin<sup>8</sup>of Texas, in an exhaustive series of studies begun as far back as 1885, undoubtedly establishes the clearest claim to the discovery of the causative agent, but in spite of his clear and concise description of the method of procedure employed, very few investigators have been able to verify the presence in dengue blood of the micrococcus which he found in such large numbers. Our lack of exact knowledge concerning the morbid anatomy of this infection
French doctors agitated over cash "bonus"
Authors: A. Dorozynski
Journal: BMJ (1998)

When the French government announced in February that each GP would receive a “bonus” of Fr9300 (£930; $1500), no one predicted the extent of the controversy this offer would create.

The bonus is to be awarded because health spending by GPs last year stayed within the budget prescribed by the French parliament to control health costs. Along with the bonus came a rise in …
PWE-070 Perspectives And Attitudes To Colonoscopy In Patients With Inflammatory Bowel Disease
Authors: C Alexakis, L Medcalf, V Chhaya, J-Y Kang, P Neild, A Poullis, R Pollok
Journal: Gut (2014)

<h3>Introduction</h3> Visualisation of mucosa at ileocolonoscopy (IC) remains the gold standard in the assessment of mucosal healing (MH) in patients with inflammatory bowel disease (IBD). MH is evolving as a key endpoint in assessing response to therapy. This will invariably mean an increased endoscopic burden on these patients. We aimed to investigate IBD patients’ perspectives on this, as well as their tolerance of IC. <h3>Methods</h3> Consecutive patients attending IBD clinic between September and December 2013 were questioned on their experience of IC. Data on sex, age, disease type (Crohn’s (CD) or ulcerative colitis (UC)), duration of illness, and no. of IC was obtained. They were asked to grade various components of the IC experience (concerns about complications, bowel preparation, disruption to life, procedure discomfort, travel to hospital) on a standardised tolerance scale from 1–5. They were also asked to qualitatively rate their overall experience of IC (not unpleasant/neither unpleasant nor pleasant/bearable/unpleasant/very unpleasant). Finally, they were asked how often they would be prepared to undertake IC in the future. <h3>Results</h3> 98 patients responded (46% male). Mean age was 43.2 years. 33 had UC, 50 had CD, and 11 were unsure of diagnosis. Mean no. IC was 3.7. 62% had a disease duration &gt;5 years, with only 4% diagnosed in the previous year. Mean tolerance scores for the group were: concerns about complications 2.6, bowel preparation 3.0, disruption to life 2.4, discomfort during procedure 3.0, travel to/from hospital 1.7. Comparisons between patient subgroups CD versus UC, age ≥55 years versus age &lt;55 years, ≥4 IC versus &lt;4 IC, and diagnosis ≥5 years versus diagnosis &lt;5 years, revealed no significant differences in scores. However, comparison between sexes showed females were more worried about the procedure than males (3.0 vs. 2.1, p = 0.02), were less tolerant of bowel preparation (3.5 vs. 2.3, p &lt; 0.001), experienced more disruption to their lives (2.9 vs. 1.9, p &lt; 0.001) and were more troubled by travel concerns (2.0 vs. 1.4, p = 0.02). The majority of the patients felt IC was bearable (53%) with only 13% describing it as very unpleasant. 55% would have the procedure as frequently as required if their physician felt it appropriate. 7% would only have IC every 5 years. <h3>Conclusion</h3> Bowel preparation and procedural discomfort are the most bothersome aspects of IC amongst IBD patients. There are clear differences in tolerance between female and male patients, and these results should prompt endoscopy units to find ways of improving patient acceptability. This could be provided in the form of a pre-test telephone consultation. A minority of patients were reluctant to increase their frequency of IC, which may be relevant in the monitoring of MH in their future management. <h3>Disclosure of Interest</h3> None Declared.
Carbon monoxide yield of cigarettes and its relation to cardiorespiratory disease.
Authors: C Borland, A Chamberlain, T Higenbottam, M Shipley, G Rose
Journal: BMJ (1983)

Estimates of the carbon monoxide yield of their cigarettes have been obtained for 4910 smokers (68% of all smokers) in the Whitehall study of men aged 40 to 64. In the 10 years after examination 635 men died. When men smoking cigarettes with high carbon monoxide yield were compared with those smoking cigarettes with a low yield, and after adjusting for age, employment grade, amount smoked, and tar yield, the risk of death was 32% lower for coronary heart disease, 49% higher for lung cancer, and 10% lower for total mortality; these differences were not statistically significant. Among men who said that they inhaled the risk of fatal coronary heart disease was 51% lower in the high carbon monoxide group (p less than 0.01), while the risk of lung cancer was 75% higher. These results provide no evidence that a smoker can reduce his risk of death by smoking a brand with a low carbon monoxide yield; he might even increase it. The complex interactions between characteristics of the smoker, smoking behaviour, constituents of tobacco smoke, and health are again demonstrated.
Transluminal Coronary Angioplasty and Intracoronary Thrombolysis: Coronary Heart Disease IV
Authors: Carl J. Pepine
Journal: JAMA (1983)

Transluminal revascularization is the subject of this book, which contains the proceedings of the Fourth International Symposium on Coronary Heart Disease held in Frankfurt, Germany, in 1982. As with any book about a new procedure, particularly one concerning transluminal coronary revascularization, the major portion of the book discusses technical aspects of the procedure. For this reason, the book is useful for a relatively small group of physicians, mainly those interested in performing transluminal coronary revascularization. The book is organized into ten major sections, including areas such as development of and experiences with transluminal angioplasty, functional results, new applications, and the use of angioplasty in peripheral and renal arteries. Each section is preceded by an article presenting an overview that is thoughtful and generally well done. Individual articles within each section are relatively brief and narrow in scope since they are limited to presentation of data and results with very brief
Narrowly Clearing the Next Hurdle — Passage of the House Reform Bill
Authors: John K. Iglehart
Journal: New England Journal of Medicine (2009)

With Democrats wielding their sizable majority to fend off strong Republican opposition and survive the defection of 39 members of their own party, the U.S. House of Representatives voted 220 to 215 to approve health care reform legislation after a day of contentious debate. On November 7, as midnight drew near, 219 House Democrats and 1 Republican (Representative Anh “Joseph” Cao of Louisiana) approved a measure that would extend insurance coverage to virtually all Americans by 2013. The 1990-page bill would also restructure private insurance, bolster primary care, and make countless other policy changes — but would not eliminate the . . .
295 Biliary leakage of fluorescent bile acids in MDR2 knockout mice: Evidence for a critical role of bile duct leakage in the pathogenesis of sclerosing cholangitis
Authors: P. Fickert, A. Fuchsbichler, M. Wagner, G. Zollner, A. Kaser, H. Tilg, R. Krause, C. Langner, K. Zatloukal, H.U. Marschall, H. Denk, M. Trauner
Journal: Journal of Hepatology (2004)
Hazards in Hyperbaric Medicine
Authors: I. McA. Ledingham, J. K. Davidson
Journal: BMJ (1969)

During the period April 1965 to April 1968 observations were made on 285 patients and 357 staff exposed to air and oxygen at pressures of 1 to 3 atmospheres absolute in a hyperbaric unit. Decompression sickness was not noted and an annual radiological skeletal survey failed to show aseptic bone necrosis; the incidence of otitic barotrauma was 4.7%. Oxygen toxicity was not observed in any patient. It is suggested that pressures in this range are relatively safe in a specialized medical hyperbaric environment.
Preliminary Report on the Clinical Use of a New Anticoagulant, Phenylindandione
Authors: ANCEL U. BLAUSTEIN, JAMES J. CROCE, MARIE ALBERIAN, NEIL RICHEY
Journal: Circulation (1950)

Heparin and dicumarol are both useful drugs but each has its limitations and accordingly search goes on for newer drugs that lack some of these limitations. A new anticoagulant, phenylindandione produces a prothrombopenia more rapidly than dicumarol and its catabolism is equally more rapid. This, therefore, aroused interest in clinical trials utilizing this new prothrombopenic agent. The drug is a light yellow, crystalline compound put up in tablet form and administered by mouth.