tbuckley/cabot-search huggingface dataset:
Antisense-Mediated Suppression of Hyaluronan Synthase 2 Inhibits the Tumorigenesis and Progression of Breast Cancer
Authors: Lishanthi Udabage, Gary R. Brownlee, Mark Waltham, Tony Blick, Emma C. Walker, Paraskevi Heldin, Susan K. Nilsson, Erik W. Thompson, Tracey J. Brown
Journal: Cancer Research (2005)

The progression of several cancers is correlated with the increased synthesis of the glycosaminoglycan, hyaluronan. Hyaluronan is synthesized at the plasma membrane by various isoforms of hyaluronan synthases (HAS). The importance of HAS2 expression in highly invasive breast cancer was characterized by the antisense inhibition of HAS2 (ASHAS2). The effect of HAS2 inhibition on cell proliferation, migration, hyaluronan metabolism, and receptor status was characterized in vitro, whereas the effect on tumorigenicity and metastasis was established in vivo. HAS2 inhibition resulted in a 24-hour lag in proliferation that was concomitant to transient arrest of 79% of the cell population in G0-G1. Inhibition of HAS2 did not alter the expression of the other HAS isoforms, whereas hyaluronidase (HYAL2) and the hyaluronan receptor, CD44, were significantly down-regulated. ASHAS2 cells accumulated greater amounts of high molecular weight hyaluronan (>10,000 kDa) in the culture medium, whereas mock and parental cells liberated less hyaluronan of three distinct molecular weights (100, 400, and 3,000 kDa). The inhibition of HAS2 in the highly invasive MDA-MB-231 breast cancer cell line inhibited the initiation and progression of primary and secondary tumor formation following s.c. and intracardiac inoculation into nude mice, whereas controls readily established both primary and secondary tumors. The lack of primary and secondary tumor formation was manifested by increased survival times where ASHAS2 animals survived 172% longer than the control animals. Collectively, these unique results strongly implicate the central role of HAS2 in the initiation and progression of breast cancer, potentially highlighting the co-dependency between HAS2, CD44, and HYAL2 expression.
Neck Sprain
Authors: Aaron A. Farbman
Journal: JAMA (1973)

One hundred thirty-six cases of uncomplicated neck sprain were studied to determine the relationship between the great disparity in duration of symptoms and various factors not directly related to the injury. The factors studied were the following: age, sex, race, occupation, marital status, hospitalization, associated medical conditions, habits, roentgenographic findings, extent of car damage, emotional factors, extensiveness of the medical history, treatment, and litigation. Only in the last four factors was there any association with the duration of symptoms that, in this study, varied from complete recovery in three days to persistence of symptoms for more than five years. This great disparity in duration of symptoms was not related to the degree of injury. As one would expect, however, the more severe the injury, the longer was the median duration of workdays lost.
Cancer of the Lung in Physicians
Authors: Ernest L. Wynder, Jerome Cornfield
Journal: New England Journal of Medicine (1953)

DURING the past two years, nine separate investigations have presented evidence that tobacco smoking is associated with the development of bronchiogenic carcinoma.1 2 3 4 5 6 7 8 9 Studies by Wynder and Graham2 and Doll and Hill,7 both based on personal interviews with over 600 patients with cancer of the lung, in particular were in close agreement quantitatively as well as qualitatively. Data on the possible relation of industrial exposures to cancer of the lung showed that although there is some evidence of a greater than average risk in some occupations, these occupations could not account for the general increase in pulmonary cancer.10 In line with . . .
Pulmonary veno-occlusive disease
Authors: David Montani, Edmund M. Lau, Peter Dorfmüller, Barbara Girerd, Xavier Jaïs, Laurent Savale, Frederic Perros, Esther Nossent, Gilles Garcia, Florence Parent, Elie Fadel, Florent Soubrier, Olivier Sitbon, Gérald Simonneau, Marc Humbert
Journal: European Respiratory Journal (2016)

Pulmonary veno-occlusive disease (PVOD) is a rare form of pulmonary hypertension (PH) characterised by preferential remodelling of the pulmonary venules. In the current PH classification, PVOD and pulmonary capillary haemangiomatosis (PCH) are considered to be a common entity and represent varied expressions of the same disease. The recent discovery of biallelic mutations in the EIF2AK4 gene as the cause of heritable PVOD/PCH represents a major milestone in our understanding of the molecular pathogenesis of PVOD. Although PVOD and pulmonary arterial hypertension (PAH) share a similar clinical presentation, with features of severe precapillary PH, it is important to differentiate these two conditions as PVOD carries a worse prognosis and life-threatening pulmonary oedema may occur following the initiation of PAH therapy. An accurate diagnosis of PVOD based on noninvasive investigations is possible utilising oxygen parameters, low diffusing capacity for carbon monoxide and characteristic signs on high-resolution computed tomography of the chest. No evidence-based medical therapy exists for PVOD at present and lung transplantation remains the preferred definitive therapy for eligible patients.
830 INFECTION AND REPLICATION OF HEPATITIS C VIRUS IN BCLC HUMAN HEPATOCELLULAR CARCINOMA CELL LINES
Authors: M. Coto-Llerena, G. Koutsoudakis, L. Boix, J.M. López-Oliva, C. Fernández, J. Bruix, X. Forns, S. Pérez-del-Pulgar
Journal: Journal of Hepatology (2012)
Absence of obesity paradox in patients with chronic heart failure and diabetes mellitus: a propensity‐matched study
Authors: Chris Adamopoulos, Philippe Meyer, Ravi V. Desai, Kyparissi Karatzidou, Fernando Ovalle, Michel White, Inmaculada Aban, Thomas E. Love, Prakash Deedwania, Stefan D. Anker, Ali Ahmed
Journal: European Journal of Heart Failure (2010)
Abstract B27: Melatonin synergistically enhances cisplatin-induced apoptosis via the dephosphorylation of ERK/p90 ribosomal S6 kinase/heat shock protein 27 in SK-OV-3 cells
Authors: Sunghoon Kim, Jihyun Kim, bonglee kim, Junghyo Kim
Journal: Clinical Cancer Research (2013)

Abstract To evaluate melatonin's ability to enhance ovarian cancer cells to cisplatin treatment for ovarian cancer, this study was performed. Melatonin by itself had no significant cytotoxicity against SK-OV-3 cells, while cisplatin suppressed the cell viability in a dose-dependent manner. Combined treatment with cisplatin and melatonin synergistically inhibited the viability of SK-OV-3 cells with the synergism between two drugs (1 &amp;gt; combination index). In contrast, melatonin revealed the protective effect against cisplatin-induced cytotoxicity in OSEN normal ovarian epithelial cells. Cotreatment with cisplatin and melatonin increased the sub-G1 DNA contents and TdT-mediated dUTP nick end-labeling (TUNEL)-positive cells compared with cisplatin control in SK-OV-3 cells, suggesting that melatonin augments cisplatin-induced apoptosis. Consistently, combined treatment of cisplatin and melatonin increased the cleavage of caspase-3 and poly-(ADP-ribose) polymerase (PARP). Importantly, melatonin synergistically inhibited the phosphorylation of extracellular signal-regulated kinase (ERK) along with dephosphorylation of 90-kDa ribosomal S6 kinase (p90RSK) and heat shock protein 27 (HSP27) induced by cisplatin. Furthermore, melatonin remarkably blocked the expression and colocalization of p90RSK and HSP27 by combination treatment with cisplatin. Taken together, our findings demonstrate that melatonin enhances cisplatin-induced apoptosis via the inactivation of ERK/p90RSK/HSP27 cascade in SK-OV-3 cells as a potent synergist to cisplatin treatment. Citation Format: Sunghoon Kim, Jihyun Kim, bonglee kim, Junghyo Kim. Melatonin synergistically enhances cisplatin-induced apoptosis via the dephosphorylation of ERK/p90 ribosomal S6 kinase/heat shock protein 27 in SK-OV-3 cells. [abstract]. In: Proceedings of the AACR Special Conference on Advances in Ovarian Cancer Research: From Concept to Clinic; Sep 18-21, 2013; Miami, FL. Philadelphia (PA): AACR; Clin Cancer Res 2013;19(19 Suppl):Abstract nr B27.
Altered anionic GBM components in monoclonal antibody against slit diaphragm-injected proteinuric rats
Authors: Yoshihide Fujigaki, Mitsumasa Nagase, Sumi Hidaka, Katsuyuki Matsui, Mikiko Shirai, Hitonari Nosaka, Hiroshi Kawachi, Fujio Shimizu, Akira Hishida
Journal: Kidney International (1998)
The G691S RET Polymorphism Increases Glial Cell Line–Derived Neurotrophic Factor–Induced Pancreatic Cancer Cell Invasion by Amplifying Mitogen-Activated Protein Kinase Signaling
Authors: Hirozumi Sawai, Yuji Okada, Kevork Kazanjian, Joseph Kim, Sascha Hasan, Oscar J. Hines, Howard A. Reber, Dave S.B. Hoon, Guido Eibl
Journal: Cancer Research (2005)

Abstract Mutations of the RET proto-oncogene are responsible for several inherited human diseases and may function as genetic modifiers of the disease. However, the role of RET mutations in pancreatic cancer has not been studied. Expression of the glial cell line–derived neurotrophic factor (GDNF) receptors RET and GDNF family receptor α1 (GFRα1) in human pancreatic cancer cells was determined by Western blot, immunofluorescence, and flow cytometry. The effect of GDNF on cell proliferation and invasion was assessed. Small interfering RNA and antibodies were used to evaluate the involvement of RET. The G691S RET polymorphism was analyzed by sequencing and restriction analysis. The modifying effect of G691S RET on GDNF-induced invasion and mitogen-activated protein kinase (MAPK) signaling was evaluated. Transfection studies with wild-type and mutated RET determined the functional role of the G691S polymorphism. Pancreatic cancer specimens and matched tissues were analyzed for the presence of the G691S RET polymorphism. GDNF receptors were found on all cell lines. GDNF increased pancreatic cancer cell proliferation and invasion, which was mediated by RET. The effect of GDNF was more profound in cells with the G691S RET polymorphism (P &amp;lt; 0.01). G691S RET correlated with an enhanced activation of the downstream extracellular signal-regulated kinase pathway. Overexpression of G691S RET increased pancreatic cancer cell invasion. The G691S RET polymorphism was also detected in human pancreatic tumors and represented a somatic mutation in some patients. These findings indicate that the G691S RET single nucleotide polymorphism may directly correlate with the aggressive growth of pancreatic cancers and may function as a genetic modifier or even low-penetrance gene. (Cancer Res 2005; 65(24): 11536-44)
Mesenchymal Precursor Cells as Adjunctive Therapy in Recipients of Contemporary Left Ventricular Assist Devices
Authors: Deborah D. Ascheim, Annetine C. Gelijns, Daniel Goldstein, Lemuel A. Moye, Nicholas Smedira, Sangjin Lee, Charles T. Klodell, Anita Szady, Michael K. Parides, Neal O. Jeffries, Donna Skerrett, Doris A. Taylor, J. Eduardo Rame, Carmelo Milano, Joseph G. Rogers, Janine Lynch, Todd Dewey, Eric Eichhorn, Benjamin Sun, David Feldman, Robert Simari, Patrick T. O’Gara, Wendy C. Taddei-Peters, Marissa A. Miller, Yoshifumi Naka, Emilia Bagiella, Eric A. Rose, Y. Joseph Woo
Journal: Circulation (2014)

Background— Allogeneic mesenchymal precursor cells (MPCs) injected during left ventricular assist device (LVAD) implantation may contribute to myocardial recovery. This trial explores the safety and efficacy of this strategy. Methods and Results— In this multicenter, double-blind, sham-procedure controlled trial, 30 patients were randomized (2:1) to intramyocardial injection of 25 million MPCs or medium during LVAD implantation. The primary safety end point was incidence of infectious myocarditis, myocardial rupture, neoplasm, hypersensitivity reaction, and immune sensitization (90 days after randomization). Key efficacy end points were functional status and ventricular function while temporarily weaned from LVAD support (90 days after randomization). Patients were followed up until transplant or 12 months after randomization, whichever came first. Mean age was 57.4 (±13.6) years, mean left ventricular ejection fraction was 18.1%, and 66.7% were destination therapy LVADs. No safety events were observed. Successful temporary LVAD weaning was achieved in 50% of MPC and 20% of control patients at 90 days ( P =0.24); the posterior probability that MPCs increased the likelihood of successful weaning was 93%. At 90 days, 3 deaths (30%) occurred in control patients, and none occurred in MPC patients. Mean left ventricular ejection fraction after successful wean was 24.0% (MPC=10) and 22.5% (control=2; P =0.56). At 12 months, 30% of MPC patients and 40% of control patients were successfully temporarily weaned from LVAD support ( P =0.69), and 6 deaths (30%) occurred in MPC patients. Donor-specific HLA sensitization developed in 2 MPC and 3 control patients and resolved by 12 months. Conclusions— In this preliminary trial, administration of MPCs appeared to be safe, and there was a potential signal of efficacy. Future studies will evaluate the potential for higher or additional doses to enhance the ability to wean LVAD recipients off support. Clinical Trial Registration— URL: http://www.clinicaltrials.gov . Unique identifier: NCT01442129.
Why can't we improve the timeliness of cancer diagnosis in children, teenagers, and young adults?
Authors: L. A. Fern, R. Birch, J. Whelan, M. Cooke, S. Sutton, R. D. Neal, C. Gerrand, G. Hubbard, S. Smith, C. Lethaby, R. Dommett, F. Gibson
Journal: BMJ (2013)

Lorna A Fern research manager , Rebecca Birch research associate , Jeremy Whelan professor of cancer medicine and clinical oncologist , Mathew Cooke lay representative , Stephen Sutton lay representative , Richard D Neal professor of primary care medicine , Craig Gerrand consultant orthopaedic surgeon, Gill Hubbard reader and co-director, Sam Smith head of nursing and quality, Chris Lethaby specialist registrar, Rachel Dommett academic clinical lecturer in paediatric oncology , Faith Gibson clinical professor of children and young people’s cancer care 11
Amyloidosis and the kidney.
Authors: H Baker
Journal: BMJ (1973)

Thank you for your interest in spreading the word about The BMJ.NOTE: We only request your email address so that the person you are recommending the page to knows that you wanted them to see it, and that it is not junk mail. We do not capture any email address. Username * Your Email * Send To * You are going to email the following Amyloidosis and the kidney. Your Personal Message CAPTCHA This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
Shc Family Expression in Neuroblastoma: High Expression of <i>shc</i>C Is Associated with a Poor Prognosis in Advanced Neuroblastoma
Authors: Elena Terui, Tadashi Matsunaga, Hideo Yoshida, Katsunori Kouchi, Hiroaki Kuroda, Tomoro Hishiki, Takeshi Saito, Shin-ichi Yamada, Hiroshi Shirasawa, Naomi Ohnuma
Journal: Clinical Cancer Research (2005)

Abstract The biological features and prognosis of neuroblastoma, a neural crest-derived pediatric tumor, are closely associated with expression of the Trk receptor. Because the Shc family proteins (ShcA, ShcB, and ShcC) are adaptors for various receptors, including Trk receptors, and are regulators of neuronal cell development, we speculated that they may play a role in neuroblastoma. Therefore, in this study, we used semiquantitative reverse transcription-PCR to examine the expression of these three genes in 15 neuroblastoma cell lines, an all-trans-retinoic acid–treated neuroblastoma cell line, and 52 tumor samples. In neuroblastoma cell lines and tumor samples, shcA was ubiquitously and highly expressed. Little expression of shcA was observed. Also, shcB was hardly expressed in neuroblastoma cell lines, but its expression in RT-BM-1 cells was enhanced after all-trans-retinoic acid–induced differentiation, and it was highly expressed in low-stage tumors (P = 0.0095). This suggests that ShcB participates in cellular differentiation and may correlate with a favorable prognosis in neuroblastoma. Finally, the expression of shcC was observed in most of the neuroblastoma cell lines and in some stage 4 patients. Patients with a high expression of shcC had a very poor prognosis (P &amp;lt; 0.0001) and amplification of MYCN, and all died within 31 months after diagnosis. Therefore, ShcC seems to be associated with an aggressive tumor phenotype, perhaps by enhancing TrkB signals. Our results suggest that the expressions of shcB and shcC are important biological factors in neuroblastoma and are useful prognostic indicators.
Observations Concerning the Production and Excretion of Cholesterol in Mammals
Authors: MEYER FRIEDMAN, SANFORD O. BYERS, BARBARA GUNNING, CLARENCE OMOTO, WARREN HAYASHI
Journal: Circulation (1954)

The possible role of the hepatic reticuloendothelial system in the synthesis as well as the disposition of endogenously produced cholesterol was studied in the rat by various means. Our results suggest that this system does not synthesize significant quantities of cholesterol nor participate in the egress of endogenously produced cholesterol from the plasma into the liver. It does however, play an important, perhaps indispensable, role in ridding blood of cholesterol derived from the diet.
Occupational Exposure to Carbofuran and the Incidence of Cancer in the Agricultural Health Study
Authors: Matthew R. Bonner, Won Jin Lee, Dale P. Sandler, Jane A. Hoppin, Mustafa Dosemeci, Michael C. R. Alavanja
Journal: Environmental Health Perspectives (2004)

Carbofuran is a carbamate insecticide registered for use on a variety of food crops including corn, alfalfa, rice, and tobacco. An estimated 5 million pounds of carbofuran is used annually in the United States, and 45% of urban African-American women have detectable levels of carbofuran in their plasma. Nitrosated carbofuran has demonstrated mutagenic properties. We examined exposure to carbofuran and several tumor sites among 49,877 licensed pesticide applicators from Iowa and North Carolina enrolled in the Agricultural Health Study. We obtained information regarding years of use, frequency of use in an average year, and when use began for 22 pesticides using self-administered questionnaires. Poisson regression was used to calculate rate ratios (RR) and 95% confidence intervals (CIs) adjusting for potential confounders. Lung cancer risk was 3-fold higher for those with > 109 days of lifetime exposure to carbofuran (RR = 3.05; 95% CI, 0.94-9.87) compared with those with < 9 lifetime exposure days, with a significant dose-response trend for both days of use per year and total years of use. However, carbofuran use was not associated with lung cancer risk when nonexposed persons were used as the referent. In addition, carbofuran exposure was not associated with any other cancer site examined. Although carbamate pesticides are suspected human carcinogens, these results should be interpreted cautiously because there was no a priori hypothesis specifically linking carbofuran to lung cancer.
K. J. R. Wightman, M.D., F.A.C.P., F.R.C.P.(C): 1914-1978
Authors: RAMSAY W. GUNTON
Journal: Annals of Internal Medicine (1978)

Editorial Notes1 June 1978K. J. R. Wightman, M.D., F.A.C.P., F.R.C.P.(C): 1914-1978RAMSAY W. GUNTON, M.D., F.A.C.P.RAMSAY W. GUNTON, M.D., F.A.C.P.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-88-6-839 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptKeith John Roy Wightman, born 12 May 1914, a Past President of the Royal College of Physicians and Surgeons of Canada, died in Toronto on Friday, 10 March 1978. He received his medical degree from the University of Toronto in 1937. After postgraduate study at Cambridge and in Toronto, he served in the Royal Canadian Army Medical Corps in Canada and North West Europe. He returned to Toronto and in 1953 was appointed Head of the Department of Therapeutics. In 1960 he became the Sir John and Lady Eaton Professor of Medicine at the University of Toronto and Physician-in-Chief of... This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 June 1978Volume 88, Issue 6Page: 839-839KeywordsSurgeons ePublished: 1 December 2008 Issue Published: 1 June 1978 Copyright & Permissions© 1978 American College of PhysiciansPDF downloadLoading ...
The contents of consciousness during sleep: Some theoretical problems
Authors: Antti Revonsuo
Journal: Behavioral and Brain Sciences (2000)

The approach of Hobson et al. is limited to the description of global states of consciousness, although more detailed analyses of the specific contents of consciousness would also be required. Furthermore, their account of the mind-brain relationship remains obscure. Nielsen's discussion suffers from conceptual and definitional unclarity. Mentation during sleep could be clarified by reconceptualizing it as an issue about the contents of consciousness. Vertes &amp; Eastman do not consider the types of memory (emotional) and learning (implicit) that are relevant during REM sleep, and therefore dismiss on inadequate grounds the possibility of memory functions associated with REM sleep. [Hobson et al.; Nielsen; Vertes &amp; Eastman]
Allergic rhinitis to grass pollen: Measurement of inflammatory mediators of mast cell and eosinophils in native nasal fluid lavage and in serum out of and during pollen season
Authors: G DILORENZO, P MANSUETO, M MELLUSO, G CANDORE, A COLOMBO, M PELLITTERI, A DRAGO, M POTESTIO, C CARUSO
Journal: Journal of Allergy and Clinical Immunology (1997)
Expanding consultant numbers is not enough
Authors: D. Flook
Journal: BMJ (1995)

EDITOR,—Trevor J Bayley suggests that the unified training grade willimprove the lot of senior house officers and registrars.1 What matters is not what they are called but whether they hold recognised posts in organised training schemes and can find jobs on accreditation.

I disagree with his statement that a simple, sudden expansion of the number of consultants can be the key to successful implementation of the system. In some specialties this may be …
The Value of 18F-FLT PET for Detecting Second Primary Cancers and Distant Metastases in Head and Neck Cancer Patients
Authors: Hiroshi Hoshikawa, Takehito Kishino, Terushige Mori, Yoshihiro Nishiyama, Yuka Yamamoto, Nozomu Mori
Journal: Clinical Nuclear Medicine (2013)

Diagnostic efficacy of (18)F-FLT PET was compared with that of (18)F-FDG PET regarding second primary cancers and distant metastases of head and neck squamous cell cancers (HNSCCs).A total of 88 patients with HNSCCs were qualitatively examined with FLT PET and FDG PET for regions of focally increased metabolism. Final diagnoses of second primary cancer and distant metastasis were established on the basis of histological findings or clinical follow-up.FDG PET had 1 false-negative finding with lung metastasis, and FLT PET had 4 false-negative findings with 1 liver metastasis, 1 bone metastasis, and 2 lung metastases. There were no false-positive findings with FLT PET in contrast to 9 with FDG PET (1 in lung, 4 in mediastinum, 1 in rectum, and 3 in stomach). Overall accuracy of FDG PET and FLT PET for pretreatment metastasis staging was 92% and 98%, respectively. Five distant metastases in 3 patients occurred after the initiation of chemoradiotherapy. FLT PET missed 2 metastatic lesions (1 in liver and 1 in lung), whereas FDG PET could not discriminate intracranial metastasis because of FDG uptake in the brain.FLT PET does not appear to be recommendable to replace FDG PET for pretreatment metastasis staging in HNSCC cases because of its lower sensitivity and higher background activity in the liver and bone marrow. However, it might provide additional diagnostic specificity and biological information.