tbuckley/cabot-search huggingface dataset:
DOCK180 Is a Rac Activator That Regulates Cardiovascular Development by Acting Downstream of CXCR4
Authors: Fumiyuki Sanematsu, Masanori Hirashima, Mélanie Laurin, Ryosuke Takii, Akihiko Nishikimi, Keiko Kitajima, Guo Ding, Mamiko Noda, Yuzo Murata, Yoshihiko Tanaka, Sadahiko Masuko, Toshio Suda, Chikara Meno, Jean-François Côté, Takashi Nagasawa, Yoshinori Fukui
Journal: Circulation Research (2010)

During embryogenesis, the CXC chemokine ligand (CXCL)12 acts on endothelial cells to control cardiac development and angiogenesis. Although biological functions of CXCL12 are exerted in part through activation of the small GTPase Rac, the pathway leading from its receptor CXC chemokine receptor (CXCR)4 to Rac activation remains to be determined.DOCK180 (dedicator of cytokinesis), an atypical Rac activator, has been implicated in various cellular functions. Here, we examined the role of DOCK180 in cardiovascular development.DOCK180 associates with ELMO (engulfment and cell motility) through the N-terminal region containing a Src homology 3 domain. We found that targeted deletion of the Src homology 3 domain of DOCK180 in mice leads to embryonic lethality with marked reduction of DOCK180 expression at the protein level. These mutant mice, as well as DOCK180-deficient mice, exhibited multiple cardiovascular abnormalities resembling those seen in CXCR4-deficient mice. In DOCK180 knocked down endothelial cells, CXCL12-induced Rac activation was impaired, resulting in a marked reduction of cell motility.These results suggest that DOCK180 links CXCR4 signaling to Rac activation to control endothelial cell migration during cardiovascular development.
The Human Immune Response to Dengue Virus Is Dominated by Highly Cross-Reactive Antibodies Endowed with Neutralizing and Enhancing Activity
Authors: Martina Beltramello, Katherine L. Williams, Cameron P. Simmons, Annalisa Macagno, Luca Simonelli, Nguyen Than Ha Quyen, Soila Sukupolvi-Petty, Erika Navarro-Sanchez, Paul R. Young, Aravinda M. de Silva, Félix A. Rey, Luca Varani, Stephen S. Whitehead, Michael S. Diamond, Eva Harris, Antonio Lanzavecchia, Federica Sallusto
Journal: Cell Host & Microbe (2010)
Abstract 5322: SOD2 enhances cell migration and invasion of tongue squamous cell carcinoma via H2O2-dependent Snail signaling
Authors: Anxun Wang, Zhonghua Liu, Su Li, Yuchen Cai, Chaoxu Zheng, Qianting He, Xiaofeng Zhou
Journal: Cancer Research (2012)

Abstract In previous studies, we demonstrated that dysregulation of manganese superoxide dismutase (SOD2) is a frequent event in tongue squamous cell carcinoma (TSCC) and is associated with lymph node metastasis. Here, we further investigated the mechanism of SOD2-mediated cell migration and invasion in paired TSCC cell lines with different metastatic potential. The UM1 and UM2 are paired cell lines from a single TSCC patient, where UM1 is more aggressive than UM2 in term of cell migration and invasion. Compared to UM2 cells, UM1 cells exhibited significantly higher SOD2 activity, increased intracellular H2O2 and higher levels of Snail, MMP-1 and pERK1/2 protein, and lower level of E-cadtherin protein. Upon knockdown of SOD2 by RNA interference, UM1 cells displayed significantly reduced cell migration and invasion abilities. This is accompanied by reductions in SOD2 activities, intracellular H2O2, levels of Snail, MMP-1 and pERK1/2 proteins, as well as increase in the level of E-cadtherin protein. Cell migration and invasion of the UM2 and the SOD2 shRNA-treated UM1 cells were enhanced by H2O2 treatment. This H2O2-mediated cell migration and invasion is accompanied by increased levels of Snail, MMP-1 and pERK1/2 protein, and decreased level of E-cadtherin protein. Thus, we conclude that the SOD2-dependent production of H2O2 contributes to both cell migration and invasion of TSCC via the Snail signaling pathway through increased Snail, MMP-1 and pERK1/2 expression, and the repression of the E-cadtherin. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 5322. doi:1538-7445.AM2012-5322
"Unacceptable" errors found in breast screening service
Authors: C. White
Journal: BMJ (2002)

The UK government's health services watchdog, the Commission for Health Improvement, has found “unacceptable and avoidable” errors in a London breast screening service.

There was no evidence of inaccurate diagnosis for the service, which achieves above average targets for cancer detection.

The problems arose in communicating the results to patients and recalling the correct patients.

The mistakes at the West of London Breast Screening Service, which is part of Hammersmith Hospitals NHS Trust, …
How to Do It: Write an obituary for the BMJ
Authors: S. Lock
Journal: BMJ (1995)

“In every individual,” wrote Dostoevsky in From the House of the Dead, “there is a spark of the Divine.” It should be the aim of every obituary to convey this spark to a reader who has never known the subject. Yet how rarely is this achieved; instead the writer falls back on prolixity, cliche, and a curriculum vitae. There is little idea of this subject's uniqueness, of how things would have been different had he or she never lived.

This is not to sneer at obituary writers or at what they produce. They have an exceptionally difficult task, and the reasons for their failure are self evident. Almost inevitably inexperienced writers confronted with an emotional task and a short deadline, they find that they knew the subject far less well than they thought. And almost inevitably they then turn to and follow published obituaries which, instead of conveying uniqueness, have relied on sentiments more appropriate to a 19th century tombstone than to a 20th century journal.

Whether conventional or justified, however, condolences for relatives are best put into a personal letter.1 Like other features in the journal, the BMJ's obituaries are primarily for readers who want their attention held in the same way as elsewhere and, as recent correspondence has confirmed,2 read them avidly. Nevertheless, for some time the editor has been faced with a paradox: whereas non-obituaries undergo rigorous peer review and have a high rejection rate, until recently obituaries did not, and most of them were published with only shortening. Given the continuing large increase in the number of doctors, the inevitable happened, with a heavy backlog of accumulated obituaries, some of them relating to doctors who had died several months previously.

What is the solution to the “problem” of the obituaries? To apply the drastic …
Oncofetal Gene<i>SALL4</i>in Aggressive Hepatocellular Carcinoma
Authors: Kol Jia Yong, Chong Gao, Joline S.J. Lim, Benedict Yan, Henry Yang, Todor Dimitrov, Akira Kawasaki, Chee Wee Ong, Kwong-Fai Wong, Sanghoon Lee, Sharada Ravikumar, Supriya Srivastava, Xi Tian, Ronnie T. Poon, Sheung Tat Fan, John M. Luk, Yock Young Dan, Manuel Salto-Tellez, Li Chai, Daniel G. Tenen
Journal: New England Journal of Medicine (2013)

Hepatocellular carcinoma is the third leading cause of cancer-related deaths worldwide. In the heterogeneous group of hepatocellular carcinomas, those with characteristics of embryonic stem-cell and progenitor-cell gene expression are associated with the worst prognosis. The oncofetal gene SALL4, a marker of a subtype of hepatocellular carcinoma with progenitor-like features, is associated with a poor prognosis and is a potential target for treatment.We screened specimens obtained from patients with primary hepatocellular carcinoma for the expression of SALL4 and carried out a clinicopathological analysis. Loss-of-function studies were then performed to evaluate the role of SALL4 in hepatocarcinogenesis and its potential as a molecular target for therapy. To assess the therapeutic effects of a peptide that targets SALL4, we used in vitro functional and in vivo xenograft assays.SALL4 is an oncofetal protein that is expressed in the human fetal liver and silenced in the adult liver, but it is reexpressed in a subgroup of patients who have hepatocellular carcinoma and an unfavorable prognosis. Gene-expression analysis showed the enrichment of progenitor-like gene signatures with overexpression of proliferative and metastatic genes in SALL4-positive hepatocellular carcinomas. Loss-of-function studies confirmed the critical role of SALL4 in cell survival and tumorigenicity. Blocking SALL4-corepressor interactions released suppression of PTEN (the phosphatase and tensin homologue protein) and inhibited tumor formation in xenograft models in vivo.SALL4 is a marker for a progenitor subclass of hepatocellular carcinoma with an aggressive phenotype. The absence of SALL4 expression in the healthy adult liver enhances the potential of SALL4 as a treatment target in hepatocellular carcinoma. (Funded by the Singapore National Medical Research Council and others.).
Contrast enhanced CT-scan to diagnose intrahepatic cholangiocarcinoma in patients with cirrhosis
Authors: Massimo Iavarone, Fabio Piscaglia, Sara Vavassori, Marzia Galassi, Angelo Sangiovanni, Laura Venerandi, Laura Virginia Forzenigo, Rita Golfieri, Luigi Bolondi, Massimo Colombo
Journal: Journal of Hepatology (2013)
Symptomatic inferior vena cava filter thrombosis: clinical study of 30 consecutive cases
Authors: B Tardy, P Mismetti, Y Page, H Decousus, A Da Costa, F Zeni, G Barral, JC Bertrand
Journal: European Respiratory Journal (1996)

Inferior vena cava (IVC) filter thrombosis has not been described as a clinical entity. Thirty patients with IVC percutaneous filter thrombosis were assessed by cavography, computed tomographic (CT) scan and/or duplex ultrasonography. All patients had proximal venous thrombosis when the filter was placed, and the indication for filter placement was a contraindication to anticoagulant therapy in eight patients (27%). Filter thrombosis occurred within 6 months following filter placement in 15 patients (early filter thrombosis group). Among these patients, 10 were not treated with oral anticoagulant, and none of the other five received adjusted anticoagulation. No patients with late filter thrombosis received anticoagulant at the time of the diagnosis. Early filter thrombosis was mainly associated with LGM filters (12 of the 15 cases). Occlusion was revealed by recurrent venous thrombosis in 18 cases. A thrombus above the filter and pulmonary embolism was found in 10 patients (33%). Thrombolytic therapy failed in 5 out of 7 cases, and all but two patients were treated with anticoagulant therapy. In conclusion, early filter thrombosis appears to be due to intracaval extension of deep vein thrombosis, and this emphasizes the need for appropriate anticoagulation. In the case of temporary contraindication to anticoagulation at the time of the filter placement, anticoagulant should be reassessed later.
Regulation of the MDM2-P53 pathway and tumor growth by PICT1 via nucleolar RPL11
Authors: Masato Sasaki, Kohichi Kawahara, Miki Nishio, Koshi Mimori, Ryunosuke Kogo, Koichi Hamada, Bunsho Itoh, Jia Wang, Yukako Komatsu, Yong Ryoul Yang, Hiroki Hikasa, Yasuo Horie, Takayuki Yamashita, Takehiko Kamijo, Yanping Zhang, Yan Zhu, Carol Prives, Toru Nakano, Tak Wah Mak, Takehiko Sasaki, Tomohiko Maehama, Masaki Mori, Akira Suzuki
Journal: Nature Medicine (2011)
Benign normolipoproteinaemic acanthocytosis.
Authors: D Lowe, R M Ibbotson, A Loizou
Journal: BMJ (1977)

~~~~Filling defect in lower pole of caccum.laparotomy mandatory.A caecal diaphragm must therefore become part of the differential diagnosis of a space-occupying lesion of the lower pole of the caecum found by radiology.The chance of diagnosing correctly a caecal diaphragm by radiology alone must be remote, but if at laparotomy for suspected pathology of the pole of the caecum faeces are palpated in the caecal pole and attempts to move them into the ascending colon fail then the presence of a caecal diaphragm must be seriously considered.
Hypertriglyceridemia and Atherosclerosis
Authors: Andrew L. Avins
Journal: Annals of Internal Medicine (1998)

Letters1 January 1998Hypertriglyceridemia and AtherosclerosisAndrew L. Avins, MD, MPHAndrew L. Avins, MD, MPHVeterans Affairs Medical Center, San Francisco; University of California, San Francisco, School of Medicine; San Francisco, CA 94121Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-128-1-199801010-00023 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail TO THE EDITOR:Dr. Ginsberg's recommendations for treatment of hypertriglyceridemia [1] are not supported by currently available evidence. First, Dr. Ginsberg offers potential biochemical rationales for how hypertriglyceridemia could cause atherosclerosis. Such explanations might be true but are an insufficient basis for establishing clinical policy. Second, he correctly notes that the observational data are inconsistent; indeed, most data do not support an independent role for hypertriglyceridemia in this process [2]. Third, he cites the Helsinki Heart Study as the primary clinical trial evidence for lowering triglyceride levels to reduce risk for coronary heart disease. However, analyses from this study showed ...References1. Ginsberg HN. Is hypertriglyceridemia a risk factor for atherosclerotic disease? A simple question with a complicated answer [Editorial]. Ann Intern Med. 1997; 126:912-4. Google Scholar2. Avins AL, Haber RJ, Hulley SB. The status of hypertriglyceridemia as a risk factor for coronary heart disease. Clin Lab Med. 1989; 9:153-68. Google Scholar3. Manninen V, Elo MO, Frick MH, Happa K, Heinonen OP, Heinsalmi P, et al. Lipid alterations and decline in the incidence of coronary heart disease in the Helsinki Heart Study. JAMA. 1988; 260:641-51. Google Scholar4. Garber AM, Avins AL. Triglyceride concentration and coronary heart disease. BMJ. 1995; 310:259-60. Google Scholar5. Physicians' Desk Reference. 49th ed. Montvale, NJ: Medical Economics Co.; 1995:1851-4. Google Scholar Author, Article, and Disclosure InformationAffiliations: Veterans Affairs Medical Center, San Francisco; University of California, San Francisco, School of Medicine; San Francisco, CA 94121 PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited byThe association between low-density lipoprotein cholesterol/high-density lipoprotein cholesterol ratio cholesterol ratio and thickened carotid intima-media thickness: A case–control studyPredictors of Plasma Triglyceride Elevation in Patients Participating in a Coronary Atherosclerosis Treatment ProgramCarbohydrate-induced hypertriacylglycerolemia: historical perspective and review of biological mechanisms 1 January 1998Volume 128, Issue 1Page: 74KeywordsAtherosclerosisCoronary heart diseaseDietDrugsHyperlipidemiaLipidsLongitudinal studiesLungsNiacinStatins Issue Published: 1 January 1998 Copyright & PermissionsCopyright © 1998 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
Different distribution of aminotrans-ferase values among healthy HCV carriers in relation to presence/absence of viremia
Authors: F. Morisco, C. Tuccillo, G. Del Vecchio Blanco, D. Leone, R. De Dominicis, G. De Luise, P. Iasevoli, G. Sessa, N. Caporaso
Journal: Journal of Hepatology (1998)
Malignant Origin of the Stromal Component of Wilms' Tumor
Authors: K. Pritchard-Jones
Journal: JNCI Journal of the National Cancer Institute (1997)

assigned to monthly or quarterly cyclic hormone therapy (2 mg of estradiol on days 1-78 and 1 mg of estradiol on days 79-84, with 1 mg of norethindrone on days 69-78) was stopped after 2-3 years of the planned 5 years of treatment because of an unacceptably high rate of endometrial pathology (including one endometrial cancer) in the quarterly compared with the monthly cycle group (6.2% versus 0.8%; P ‫ס‬ .004).Although this study used different hormones than those in the U.S. trial, it raises questions about the safety of quarterly cyclic therapy.Current hormone replacement regimens might be safe, but are they optimal?For short-term treatment of menopausal symptoms, MPA appears safe and effective.However, growing evidence suggests that micronized progesterone might be a better progestin for long-term use.Neither MPA nor progesterone added to estrogen alters the beneficial effect of estrogen in preventing loss of bone density ( 8), but evidence suggests that MPA negates more of the beneficial effects of estrogen on the cardiovascular system than micronized progesterone.MPA reduces the high-density lipoprotein-increasing effect of unopposed estrogen more than micronized progesterone does (9) and may reduce the beneficial effect on atherosclerosis (10) and on coronary vascular tone (11,12).The PEPI Trial found no increased risk of endometrial hyperplasia in women who were randomly assigned to cyclic therapy with daily conjugated estrogens plus micronized progesterone given at a dose of 200 mg daily for 10 days per month, but no studies of the effect of micronized progesterone on endometrial cancer risk have been published.
Avoid prescribing antibiotics in acute rhinosinusitis
Authors: Wytske J Fokkens, Ruth Hoffmans, Mike Thomas
Journal: BMJ (2014)

Change Page aims to alert clinicians to the immediate need for a change in practice to make it consistent with current evidence. The series advisers are Sera Tort, clinical editor, and David Tovey, editor in chief, the Cochrane Library. We welcome any suggestions for future articles (changepage@bmj.com).
Ovarian Hormones Increase IL-17A Production from Th17 Cells through an IL-23R and Let-7f Mediated Pathway in Severe Asthma
Authors: Dawn C. Newcomb, Jacqueline-Yvonne Cephus, R. Stokes Peebles, Daniel E. Dulek, Madison Boswell, Emily W. Langley, Amy S. Feldman, John M. Fahrenholz, Weisong Zhou, Kasia Goleniewska
Journal: Journal of Allergy and Clinical Immunology (2015)
Hepatocellular Carcinoma Confirmation, Treatment, and Survival in Surveillance, Epidemiology, and End Results Registries, 1992-2008
Authors: Sean F. Altekruse, Katherine A. McGlynn, Lois A. Dickie, David E. Kleiner
Journal: Hepatology (2011)

Approaches to the diagnosis and management of hepatocellular carcinoma (HCC) are improving survival. In the Surveillance, Epidemiology, and End Results-13 registries, HCC stage, histological confirmation, and first-course surgery were examined. Among 21,390 HCC cases diagnosed with follow-up of vital status during 1998-2008, there were 4,727 (22%) with reported first-course invasive liver surgery, local tumor destruction, or both. The proportion with reported liver surgery or ablation was 39% among localized stage cases and only 4% among distant/unstaged cases. Though 70% of cases had histologically confirmed diagnoses, the proportion with confirmed diagnoses was higher among cases with reported invasive surgery (99%), compared to cases receiving ablation (81%) or no reported therapy (65%). Incidence rates of histologically unconfirmed HCC increased faster than those of confirmed HCC from 1992 to 2008 (8% versus 3% per year). Two encouraging findings were that incidence rates of localized-stage HCC increased faster than rates of regional- and distant-stage HCC combined (8% versus 4% per year), and that incidence rates of reported first-course surgery or tumor destruction increased faster than incidence rates of HCC without such therapy (11% versus 7%). Between 1975-1977 and 1998-2007, 5-year cause-specific HCC survival increased from just 3% to 18%. Survival was 84% among transplant recipients, 53% among cases receiving radiofrequency ablation at early stage, 47% among cases undergoing resection, and 35% among cases receiving local tumor destruction. Asian or Pacific Islander cases had significantly better 5-year survival (23%) than white (18%), Hispanic (15%), or black cases (12%).
Pseudohyperkalemia in Acute Myelocytic Leukemia
Authors: L. C. Chumbley
Journal: JAMA (1970)

The occurrence of pseudohyperkalemia in acute myelocytic leukemia is, to the author's knowledge, previously undescribed. Pseudohyperkalemia may be caused by release of potassium from platelets or white blood cells during coagulation. The precise mechanisms responsible for these occurrences are not known.
Association of Rhinovirus Infection with Increased Disease Severity in Acute Bronchiolitis
Authors: Nikolaos G. Papadopoulos, Maria Moustaki, Mariza Tsolia, Apostolos Bossios, Eleni Astra, Anargiroula Prezerakou, Dimitrios Gourgiotis, Dimitrios Kafetzis
Journal: American Journal of Respiratory and Critical Care Medicine (2002)

Respiratory syncytial virus (RSV) is the major pathogen responsible for acute bronchiolitis in infancy. However, evaluation of the relative importance of rhinovirus or multiple viral infections has been hampered by the lack of sensitive diagnostic methodologies. Therefore, in this study we used the reverse transcription-polymerase chain reaction for 11 respiratory pathogens to assess the etiology in infants with acute bronchiolitis and correlate it with clinical characteristics of the disease. Viruses were detected in 73.7% of patients. RSV was identified in 72.4% of virologically confirmed cases, rhinovirus in 29%, whereas multiple infections represented 19.5% of cases, most of which (69%) were combinations of rhinovirus with RSV. In a logistic regression model controlling for age, sex, birth weight, presence of fever, and day of disease on admission, the presence of rhinovirus was found to increase by approximately five-fold, the risk for severe disease. Multiple pathogens had a similar trend in the univariate analysis, which was eliminated in the multivariate model. Multiple virus cases were admitted to the hospital later in the course of their disease than unique pathogen cases, suggesting successive infections. In conclusion, rhinovirus is second only to RSV as a causative agent of bronchiolitis and is associated with more severe disease. The presence of more than one pathogen may influence the natural history of acute bronchiolitis.
Treatment of Papilloma of Bladder with Radioactive Colloidal Gold Au198
Authors: F. Ellis, R. Oliver
Journal: BMJ (1955)

This report describes an investigation designed to compare vaccination with B.C.G. and vole bacillus vaccines, and records the preliminary results after one and two years.The B.C.G. was given in the routine intradermal manner and the vole vaccine by multiple puncture to those of 5 years and over and intradermally to those under 5 years.Vaccination by the multiplepuncture method is probably slower than by intra- dermal injection, but it is considered to be the method of choice and is simpler and more certain in young children.The rate of conversion after vole vaccination is a little slower than after B.C.G., but the percentages- 95% after six weeks and 100% after twelve weeks- are very satisfactory, and compare closely with those obtained with B.C.G.We believe that vaccination with vole bacillus has certain advantages because of the milder clinical course and the smaller rate of reversions.The periodic surveys showed that induration developed in a substantial proportion of the cases receiving vole vaccine by the multiple-puncture method, and that, later, lupoid reactions occurred in the vaccination area.These later complications were noted in 5% and 15% of the cases inspected after the first and second years.The discovery of lupoid reactions at the second yearly in- spection in arms regarded as healed at the first yearly inspection was unexpected and unfortunate, and we regard the rate of these reactions to be too high to permit of the routine use of the vaccine until these diffi- culties have been overcome.
Photoselective Vaporization (PVP) versus Transurethral Resection of the Prostate (TURP): A Prospective Bi-Centre Study of Perioperative Morbidity and Early Functional Outcome
Authors: Alexander Bachmann, Leander Schürch, Robin Ruszat, Stephen F. Wyler, Hans-Helge Seifert, Alexander Müller, Kurt Lehmann, Tullio Sulser
Journal: European Urology (2005)